The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp...The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.展开更多
The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,...The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.展开更多
The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
BACKGROUND Ras-related protein Rab24,which belongs to the small GTPase family,plays a crucial role in regulating intracellular protein trafficking.Dysregulation of Rab24 has been recently identified in hepatocellular ...BACKGROUND Ras-related protein Rab24,which belongs to the small GTPase family,plays a crucial role in regulating intracellular protein trafficking.Dysregulation of Rab24 has been recently identified in hepatocellular carcinoma(HCC).However,its clinical significance and tumor related effects remain to be further clarified.AIM To explore the expression pattern of Rab24 and its role in HCC progression.METHODS The expression profile of Rab24 was tested in HCC tissues together with adjacent tissues from transcriptional,mRNA,and protein levels.The prognostic role of Rab24 in HCC was assessed by univariate and multivariate analyses.Clinical outcomes were evaluated by the Kaplan-Meier analysis and log-rank test.The effect of Rab24 on cell proliferation was tested through cellular experiments and xenograft experiments.RESULTS Rab24 expression was elevated in HCC tissues compared to adjacent liver tissues.High expression of Rab24 was significantly associated with larger tumor size and advanced tumor stage.Moreover,HCC patients with high Rab24 expression showed poorer overall survival,and Rab24 was identified as an independent prognosis factor according to multivariate analysis.By using overexpression and shRNA knockdown strategies in HCC cell lines,we found that Rab24 can promote HCC proliferation.Finally,we validated that silencing Rab24 significantly attenuated xenograft growth in vivo.CONCLUSION Our study demonstrated that high expression of Rab24 was significantly correlated with poorer prognosis of HCC patients,indicating the potential of Rab24 as a novel clinical biomarker and therapeutic target.展开更多
BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role o...BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role of MEX3A in hepatocellular carcinoma(HCC)remains largely unexplored,with limited reports available in the literature.AIM To investigate expression and clinical significance of MEX3A in HCC and explore its potential role in tumor progression.METHODS We analyzed MEX3A mRNA expression in HCC and adjacent tissues using data from The Cancer Genome Atlas(TCGA).The correlation between MEX3A expression and overall survival(OS)was evaluated.Immunohistochemistry was performed on HCC surgical specimens to validate MEX3A expression and its association with clinical parameters,including hepatitis B virus(HBV)positivity,tumor differentiation and tumor size.Additionally,MEX3A knockdown HCC cell lines were constructed to explore the biological functions of MEX3A.Cell prolif-eration was assessed using cell counting kit-8 and clone formation assays,while cell cycle progression was analyzed by flow cytometry.The effects of MEX3A on the Wnt/β-catenin signaling pathway were examined by western blotting and immunofluorescence.Cell migration was evaluated using scratch and Transwell assays.Finally,the role of the transcription factor RORA in mediating MEX3A effects was explored by silencing RORA and analyzing its impact on cell proliferation and protein expression.RESULTS TCGA data analysis revealed that MEX3A mRNA expression was significantly higher in HCC tissues compared to adjacent tissues.Higher MEX3A expression was associated with poorer OS.These findings were validated in HCC surgical specimens.Immunohistochemistry confirmed elevated MEX3A expression in HCC tissues and showed positive correlations with Ki-67 and vimentin levels.MEX3A expression was closely related to HBV positivity,tumor differentiation and tumor size.Mechanistic studies demonstrated that MEX3A knockdown inhibited cell proliferation and cell cycle progression,as shown by reduced expression ofβ-catenin,c-Myc and cyclin D1.Additionally,MEX3A knockdown inhibited the nuclear entry ofβ-catenin,thereby suppressing the activation of downstream oncogenic pathways.MEX3A depletion significantly reduced the migratory ability of HCC cells,likely through downregulation of the epithelial-mesenchymal transition pathway.Transcription factor analysis identified RORA as a potential mediator of MEX3A effects.Silencing RORA antagonized the effects of MEX3A on cell proliferation and the expression ofβ-catenin,c-Myc and cyclin D1.CONCLUSION MEX3A promotes cell proliferation in HCC by regulating the RORA/β-catenin pathway.Our findings suggest that MEX3A could serve as a prognostic marker and therapeutic target for HCC.展开更多
The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,N...The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.展开更多
Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplas...Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.展开更多
BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully unde...BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.AIM To investigate the roles and mechanisms of SERPINB5 in rectal cancer.METHODS SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis.SW480 cells were transfected with pcDNASERPINB5 or short-hairpin RNA targeting SERPINB5(sh-SERPINB5).Cell proliferation,invasion,and apoptosis were then evaluated.The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1(HSP90AA1)was confirmed through a co-immunoprecipitation assay.Subsequently,pcDNAHSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells,and cell progression was then detected.Moreover,rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression.Additionally,sh-SERPINB5-transfected SW480 cells were implanted into nude mice,and xenograft tumor growth was then evaluated.RESULTS SERPINB5 was prominently upregulated in rectal cancer tissues and cells.SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis.In contrast,SERPINB5 knockdown had the opposite effects.Moreover,SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells.HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis.By contrast,HSP90AA1 knockdown suppressed cell progression.The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression.Additionally,SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.CONCLUSION SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.展开更多
Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous ...Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.展开更多
The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exert...The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.展开更多
Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal mus...Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.展开更多
Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interfe...Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.展开更多
BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogen...BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.展开更多
Hepatocellular carcinoma(HCC),a common malignancy worldwide,still lacks effective clinical treatment.The study aimed to investigate the oncogenes that affect the progression of HCC and their possible mechanisms.In our...Hepatocellular carcinoma(HCC),a common malignancy worldwide,still lacks effective clinical treatment.The study aimed to investigate the oncogenes that affect the progression of HCC and their possible mechanisms.In our study,we initially confirmed a higher level of PRDX2 in the bile of HCC patients compared to those with choledocholithiasis by 2-DE,LC-MS,and ELISA.Subsequently,we demonstrated the high expression of peroxiredoxin 2(PRDX2)in HCC based on the TCGA database and clinical sample analysis.Furthermore,PRDX2 overexpression enhanced the viability of HCC cells.And PRDX2 silencing induced senescence of HCC cells.In vivo,knockdown of PRDX2 significantly reduced the weight of xenograft tumors.PRDX2 also was found to activate the Wnt/β-catenin pathway by inducingβ-catenin nuclear translocation.Consequently,we proved that silencing PRDX2 could inhibit proliferation and Wnt/β-catenin pathway while promoting senescence in HCC cells.展开更多
An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(...An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.展开更多
BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPI...BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.展开更多
Background The proliferation of porcine ovarian granulosa cells(GCs)is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis.Previous studies foun...Background The proliferation of porcine ovarian granulosa cells(GCs)is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis.Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1(UCHL1)regulates female reproduction,especially in ovarian development.However,the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear.Results UCHL1 overexpression promoted GC proliferation,and knockdown had the opposite effect.UCHL1 is directly bound to cyclin B1(CCNB1),prolonging the half-life of CCNB1 and inhibiting its degradation,thereby promoting GC proliferation.What's more,a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs.Conclusions UCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1,and isovitexin enhanced the enzyme activity of UCHL1.These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development.展开更多
Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hap...Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.展开更多
Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser captu...Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.展开更多
As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear...As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear.According to transcriptome data,we identified PbGIF1was highly expressed during fruit development in cytokinins induced parthenocarpy pear.In the present study,the biofunction of PbGIF1 was initially verified.Overexpression of PbGIF1 promoted fruit size of transgenic tomato.The size of flesh fruit was not affected by cell expansion but the cell proliferation was promoted by overexpressing Pb GIF1.The accelerated cell proliferation process was also observed in PbGIF1-overexpressed transgenic pear fruit calli.The transcriptional regulation of cytokinins on PbGIF1 was further confirmed by exogenous CPPU treatments in pear fruitlets.To investigate the underlying mechanism,the cytokinins-responded factor,PbRR1,was further focused on.The results of Yeast-one-hybrid assay suggested that PbRR1 can bind to the promoter sequence of PbGIF1.The transcriptional activation of PbRR1 on PbGIF1 was also confirmed by Dual-Luciferase assays.Taken together,the results showed that cytokinins control pear fruit development via the transcriptional activation of PbGIF1 by PbRR1.展开更多
文摘The published article titled“lncRNA FEZF1-AS1 Is Associated with Prognosis in Lung Adenocarcinoma and Promotes Cell Proliferation,Migration,and Invasion”has been retracted from Oncology Research,Vol.27,No.1,2019,pp.39–45.
文摘The published article titled“Procaine inhibits the proliferation and migration of colon cancer cells through inactivation of the ERK/MAPK/FAK pathways by regulation of RhoA”has been retracted from Oncology Research,Vol.26,No.2,2018,pp.209–217.
文摘The published article titled“Puerarin inhibits proliferation and induces apoptosis by upregulation of miR-16 in bladder cancer cell line T24”has been retracted from Oncology Research,Vol.26,No.8,2018,pp.1227–1234.
文摘BACKGROUND Ras-related protein Rab24,which belongs to the small GTPase family,plays a crucial role in regulating intracellular protein trafficking.Dysregulation of Rab24 has been recently identified in hepatocellular carcinoma(HCC).However,its clinical significance and tumor related effects remain to be further clarified.AIM To explore the expression pattern of Rab24 and its role in HCC progression.METHODS The expression profile of Rab24 was tested in HCC tissues together with adjacent tissues from transcriptional,mRNA,and protein levels.The prognostic role of Rab24 in HCC was assessed by univariate and multivariate analyses.Clinical outcomes were evaluated by the Kaplan-Meier analysis and log-rank test.The effect of Rab24 on cell proliferation was tested through cellular experiments and xenograft experiments.RESULTS Rab24 expression was elevated in HCC tissues compared to adjacent liver tissues.High expression of Rab24 was significantly associated with larger tumor size and advanced tumor stage.Moreover,HCC patients with high Rab24 expression showed poorer overall survival,and Rab24 was identified as an independent prognosis factor according to multivariate analysis.By using overexpression and shRNA knockdown strategies in HCC cell lines,we found that Rab24 can promote HCC proliferation.Finally,we validated that silencing Rab24 significantly attenuated xenograft growth in vivo.CONCLUSION Our study demonstrated that high expression of Rab24 was significantly correlated with poorer prognosis of HCC patients,indicating the potential of Rab24 as a novel clinical biomarker and therapeutic target.
基金Supported by Suzhou Municipal Science and Technology Bureau,No.SYS2020081.
文摘BACKGROUND MEX3A is a member of the human homologous gene MEX-3 family.It has been shown to promote cell proliferation and migration in various cancers,indicating its potential clinical significance.However,the role of MEX3A in hepatocellular carcinoma(HCC)remains largely unexplored,with limited reports available in the literature.AIM To investigate expression and clinical significance of MEX3A in HCC and explore its potential role in tumor progression.METHODS We analyzed MEX3A mRNA expression in HCC and adjacent tissues using data from The Cancer Genome Atlas(TCGA).The correlation between MEX3A expression and overall survival(OS)was evaluated.Immunohistochemistry was performed on HCC surgical specimens to validate MEX3A expression and its association with clinical parameters,including hepatitis B virus(HBV)positivity,tumor differentiation and tumor size.Additionally,MEX3A knockdown HCC cell lines were constructed to explore the biological functions of MEX3A.Cell prolif-eration was assessed using cell counting kit-8 and clone formation assays,while cell cycle progression was analyzed by flow cytometry.The effects of MEX3A on the Wnt/β-catenin signaling pathway were examined by western blotting and immunofluorescence.Cell migration was evaluated using scratch and Transwell assays.Finally,the role of the transcription factor RORA in mediating MEX3A effects was explored by silencing RORA and analyzing its impact on cell proliferation and protein expression.RESULTS TCGA data analysis revealed that MEX3A mRNA expression was significantly higher in HCC tissues compared to adjacent tissues.Higher MEX3A expression was associated with poorer OS.These findings were validated in HCC surgical specimens.Immunohistochemistry confirmed elevated MEX3A expression in HCC tissues and showed positive correlations with Ki-67 and vimentin levels.MEX3A expression was closely related to HBV positivity,tumor differentiation and tumor size.Mechanistic studies demonstrated that MEX3A knockdown inhibited cell proliferation and cell cycle progression,as shown by reduced expression ofβ-catenin,c-Myc and cyclin D1.Additionally,MEX3A knockdown inhibited the nuclear entry ofβ-catenin,thereby suppressing the activation of downstream oncogenic pathways.MEX3A depletion significantly reduced the migratory ability of HCC cells,likely through downregulation of the epithelial-mesenchymal transition pathway.Transcription factor analysis identified RORA as a potential mediator of MEX3A effects.Silencing RORA antagonized the effects of MEX3A on cell proliferation and the expression ofβ-catenin,c-Myc and cyclin D1.CONCLUSION MEX3A promotes cell proliferation in HCC by regulating the RORA/β-catenin pathway.Our findings suggest that MEX3A could serve as a prognostic marker and therapeutic target for HCC.
文摘The published article titled“Overexpression of long noncoding RNA PTENP1 inhibits cell proliferation and migration via suppression of miR-19b in breast cancer cells”has been retracted from Oncology Research,Vol.26,No.6,2018,pp.869–878.
基金supported by the National Natural Science Foundation of China (32060755)Natural Science Foundation of Inner Mongolia (2024MS03001)+7 种基金Inner Mongolia Autonomous Region Open Competition Projects (2022JBGS0018)Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (NJYT23090)Inner Mongolia Autonomous Region Science and Technology Leading Team (2022LJRC0006)Inner Mongolia Autonomous Region Science and Technology Major Project (2021ZD0009)Major Agricultural Science and Technology Project of the Ministry of Agriculture and Rural Affairs (NK2022130203)Central Government Guides Local Science and Technology Development Funds (2022ZY0212)Inner Mongolia Autonomous Region High-level Talent Support ProgramInner Mongolia University Chief Scientist Program。
文摘Somatic cell nuclear transfer(SCNT)has been successfully employed across various mammalian species,yet cloned animals consistently exhibit low pregnancy rates,primarily due to placental abnormalities such as hyperplasia and hypertrophy.This study investigated the involvement of the Hippo signaling pathway in aberrant placentaldevelopmentinSCNT-inducedbovine pregnancies.SCNT-derived cattle exhibited placental hypertrophy,including enlarged abdominal circumference and altered placental cotyledon morphology.RNA sequencing analysis indicated significant dysregulation of Hippo signaling pathway genes in SCNT placentas.Coexpression of YAP1 and CCND1 was observed in cloned blastocysts,placental tissues,and bovine placental mesenchymal stem cells(bPMSCs).Manipulation of YAP1expression demonstrated the capacity to regulate bPMSC proliferation.Experimental assays confirmed the direct binding of YAP1 to CCND1,which subsequently promoted CCND1 expression in bPMSCs.Furthermore,inhibition of CDK6,a downstream target of CCND1,attenuated SCNT bPMSC proliferation.This study identified YAP1 as a key regulatory component within the Hippo signaling pathway that drives placental hyperplasia in cloned cattle through up-regulation of CCND1-CDK6 expression,facilitating cell cycle progression.These findings offer potential avenues for enhancing cloning efficiency,with implications for evolutionary biology and the conservation of valuable germplasm resources.
基金Supported by the Medical Science Research Project Plan of the Hebei Provincial Health Commission,No.20210027.
文摘BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.AIM To investigate the roles and mechanisms of SERPINB5 in rectal cancer.METHODS SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis.SW480 cells were transfected with pcDNASERPINB5 or short-hairpin RNA targeting SERPINB5(sh-SERPINB5).Cell proliferation,invasion,and apoptosis were then evaluated.The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1(HSP90AA1)was confirmed through a co-immunoprecipitation assay.Subsequently,pcDNAHSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells,and cell progression was then detected.Moreover,rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression.Additionally,sh-SERPINB5-transfected SW480 cells were implanted into nude mice,and xenograft tumor growth was then evaluated.RESULTS SERPINB5 was prominently upregulated in rectal cancer tissues and cells.SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis.In contrast,SERPINB5 knockdown had the opposite effects.Moreover,SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells.HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis.By contrast,HSP90AA1 knockdown suppressed cell progression.The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression.Additionally,SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.CONCLUSION SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.
基金supported by the National Natural Science Foundation of China,Nos.81672261(to XH),81972151(to HZ),82372568(to JL)the Natural Science Foundation of Guangdong Province,Nos.2019A1515011106(to HZ),2023A1515030080(to JL)。
文摘Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81973377,81903689,82073906 and 82273987)the Key Natural Science Foundation of Jiangsu Higher Education Institutions of China(Grant Nos.:19KJB350006 and 19KJA460008)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),the initializing Fund of Xuzhou Medical University(Grant No.:D2018011)Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX21-2733 and KYCX22-2966).
文摘The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.However,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.
基金supported by the National Natural Science Foundation of China,Nos.82171172(to RZ)and 81771366(to RZ)Fundamental Research Funds for the Central Universities of Central South University,Nos.2021zzts1095(to SZ)and 2022zzts0832(to HY)。
文摘Mutations in the microrchidia CW-type zinc finger protein 2(MORC2)gene are the causative agent of Charcot-Marie-Tooth disease type 2Z(CMT2Z),and the hotspot mutation p.S87L is associated with a more seve re spinal muscular atrophy-like clinical phenotype.The aims of this study were to determine the mechanism of the severe phenotype caused by the MORC2 p.S87L mutation and to explore potential treatment strategies.Epithelial cells were isolated from urine samples from a spinal muscular atrophy(SMA)-like patient[MORC2 p.S87L),a CMT2Z patient[MORC2 p.Q400R),and a healthy control and induced to generate pluripotent stem cells,which were then differentiated into motor neuron precursor cells.Next-generation RNA sequencing followed by KEGG pathway enrichment analysis revealed that differentially expressed genes involved in the PI3K/Akt and MAP K/ERK signaling pathways were enriched in the p.S87L SMA-like patient group and were significantly downregulated in induced pluripotent stem cells.Reduced proliferation was observed in the induced pluripotent stem cells and motor neuron precursor cells derived from the p.S87L SMA-like patient group compared with the CMT2Z patient group and the healthy control.G0/G1 phase cell cycle arrest was observed in induced pluripotent stem cells derived from the p.S87L SMA-like patient.MORC2 p.S87Lspecific antisense oligonucleotides(p.S87L-ASO-targeting)showed significant efficacy in improving cell prolife ration and activating the PI3K/Akt and MAP K/ERK pathways in induced pluripotent stem cells.Howeve r,p.S87L-ASO-ta rgeting did not rescue prolife ration of motor neuron precursor cells.These findings suggest that downregulation of the PI3K/Akt and MAP K/ERK signaling pathways leading to reduced cell proliferation and G0/G1 phase cell cycle arrest in induced pluripotent stem cells might be the underlying mechanism of the severe p.S87L SMA-like phenotype.p.S87L-ASO-targeting treatment can alleviate disordered cell proliferation in the early stage of pluripotent stem cell induction.
基金supported by the Gusu Medical Key Talent Project of Suzhou City of China(GSWS2020005)the New Pharmaceutics and Medical Apparatuses Project of Suzhou City of China(SLJ2021007)+3 种基金the Suzhou City Key Clinical Disease Diagnosis and Treatment Technology Special Project,China(LCZX202129)Wujiang Science and Educational Health Revitalization Fund Project,Suzhou,China(WWK202015)the Scientific Research Project of Suzhou Ninth People’s Hospital,Suzhou,China(YK202008)and Suzhou“Science and Education”Youth Science and Technology Project,Suzhou,China(KJXW2020075).
文摘Colorectal cancer(CRC)stands among the top prevalent cancers worldwide and holds a prominent position as a major contributor to cancer-related mortality globally.Absent in melanoma 2(AIM2),a constituent of the interferoninducible hematopoietic interferon-inducible nuclear antigens with 200 amino acid repeats protein family,contributes to both cancer progression and inflammasome activation.Despite this understanding,the precise biological functions and molecular mechanisms governed by AIM2 in CRC remain elusive.Consequently,this study endeavors to assess AIM2’s expression levels,explore its potential antitumor effects,elucidate associated cancer-related processes,and decipher the underlying signaling pathways in CRC.Our findings showed a reduced AIM2 expression in most CRC cell lines.Elevation of AIM2 levels suppressed CRC cell proliferation and migration,altered cell cycle by inhibiting G1/S transition,and induced cell apoptosis.Further research uncovered the participation of P38 mitogen-activated protein kinase(P38MAPK)in AIM2-mediated modulation of CRC cell apoptosis and proliferation.Altogether,our achievements distinctly underscored AIM2’s antitumor role in CRC.AIM2 overexpression inhibited proliferation and migration and induced apoptosis of CRC cells via activating P38MAPK signaling pathway,indicating AIM2 as a prospective and novel therapeutic target for CRC.
文摘BACKGROUND Pancreatic cancer,a formidable gastrointestinal neoplasm,is characterized by its insidious onset,rapid progression,and resistance to treatment,which often lead to a grim prognosis.While the complex pathogenesis of pancreatic cancer is well recognized,recent attention has focused on the oncogenic roles of senescent tumor-associated fibroblasts.However,their precise role in pancreatic cancer remains unknown.Resveratrol is a natural polyphenol known for its multifaceted biological actions,including antioxidative and neuroprotective properties,as well as its potential to inhibit tumor proliferation and migration.Our current investigation builds on prior research and reveals the remarkable ability of resveratrol to inhibit pancreatic cancer proliferation and metastasis.AIM To explore the potential of resveratrol in inhibiting pancreatic cancer by targeting senescent tumor-associated fibroblasts.METHODS Immunofluorescence staining of pancreatic cancer tissues revealed prominent coexpression ofα-SMA and p16.HP-1 expression was determined using immunohistochemistry.Cells were treated with the senescence-inducing factors known as 3CKs.Long-term growth assays confirmed that 3CKs significantly decreased the CAF growth rate.Western blotting was conducted to assess the expression levels of p16 and p21.Immunofluorescence was performed to assess LaminB1 expression.Quantitative real-time polymerase chain reaction was used to measure the levels of several senescence-associated secretory phenotype factors,including IL-4,IL-6,IL-8,IL-13,MMP-2,MMP-9,CXCL1,and CXCL12.A scratch assay was used to assess the migratory capacity of the cells,whereas Transwell assays were used to evaluate their invasive potential.RESULTS Specifically,we identified the presence of senescent tumor-associated fibroblasts within pancreatic cancer tissues,linking their abundance to cancer progression.Intriguingly,Resveratrol effectively eradicated these fibroblasts and hindered their senescence,which consequently impeded pancreatic cancer progression.CONCLUSION This groundbreaking discovery reinforces Resveratrol's stature as a potential antitumor agent and positions senescent tumor-associated fibroblasts as pivotal contenders in future therapeutic strategies against pancreatic cancer.
基金National Nature Science Foundation of China(Nos.81960118,81860115,81760116 and 82060116)Guizhou Science and Technology Project:Qiankehe Foundation(No.(2020)1Y300)+8 种基金Natural Science Foundation of Sichuan(No.2022NSFSC0837)Science and Technology Project of Chengdu(No.2022-YF05-01811-SN)Science and Technology Project of Guizhou Province(No.YQK(2023)032)Guizhou Medical University Doctoral Start-Up Fund(No.gyfybsky-2021-27)Guizhou Medical University Doctoral Start-Up Fund(No.gyfybsky-2021-26)Guizhou Science and Technology Department(No.(2019)1259)Guizhou Science and Technology Department Guizhou Science and Technology Platform Talents(No.(2017)5718)Science and Technology Fund of Guizhou Provincial Health Commission(No.gzwki2021-382)The Affiliated Hospital of Guizhou Medical University Excellent Reserve Talent in 2023(No.gyfyxkrc-2023-06).
文摘Hepatocellular carcinoma(HCC),a common malignancy worldwide,still lacks effective clinical treatment.The study aimed to investigate the oncogenes that affect the progression of HCC and their possible mechanisms.In our study,we initially confirmed a higher level of PRDX2 in the bile of HCC patients compared to those with choledocholithiasis by 2-DE,LC-MS,and ELISA.Subsequently,we demonstrated the high expression of peroxiredoxin 2(PRDX2)in HCC based on the TCGA database and clinical sample analysis.Furthermore,PRDX2 overexpression enhanced the viability of HCC cells.And PRDX2 silencing induced senescence of HCC cells.In vivo,knockdown of PRDX2 significantly reduced the weight of xenograft tumors.PRDX2 also was found to activate the Wnt/β-catenin pathway by inducingβ-catenin nuclear translocation.Consequently,we proved that silencing PRDX2 could inhibit proliferation and Wnt/β-catenin pathway while promoting senescence in HCC cells.
基金The Fund of National Cancer Center Research and Development(26-A-4),The Grants-in-Aid for Scientific Research(Grant Nos.15K10451,16K10866 and 16K20063)from Japan Society for the Promotion of Science.
文摘An important factor in the emergence and progre sion of osteosarcoma(OS)is the dysregulated expression of microRNAs(miRNAs).Transcription factor 7-like 1(TCF7LI),a member of the T cell factor/lymphoid enhancer factor(TCF/LEF)transcription factor family,interacts with the Wnt signaling pathway regulator β-catenin and acts as a DNA-specific binding protein.This study sought to elucidate the impact of the interaction between miR 3293p and TCF7L1 on.the growth and apoptosis of OS and analyze the regulatory expression relationship between miRNA and mRNA in osteosarcoma cells using a variety of approaches.MiR329-3p was significantly downregulated,while TCF7L1 was considerably up-regulated in all examined OS cell lines.Additionally,a clinical comparison study was performed using the TCGA database.Subsequently,the regulatory relationship between miR-329-3p and TCF7L1 on the proliferation and apoptosis of OS cells was verified through in vitro and in vivo experiments.When miR 329-3p was transfected into the OS cell line,the expression of TCF7L1 decreased,the proliferation of OS cells was inhibited,the cytoskeleton disintegrated,and the nucleus condensed to fom apoptotic bodies.The expression of proteins that indicate apoptosis increased simultaneously.The cell cycle was arrested in the G0/G1 phase,and the G1/S transition was blocked.The introduction of miR 3293p also inhibited downstream Cyclin D1 of the Wnt pathway.Xenograf experiments indicated that the overexpression of miR-329-3p signi ficanly inhibited the growth of OS xenografts in nude mice,and the expression of TCF7L1 and C-Myc in tumor tssues decreased.MiR 329-3p was significantly reduced in OS cells and played a suppressive role in tumorigenesis and proliferation by targeting TCF7L1 both in vitro and in vivo.Osteosarcoma cell cycle arrest and pathway inhibition were observed upon the regulation of TCF7LI by miR 3293p.Summarizing these results,it can be inferred that miR.3293p exerts anticancer efects in osteosarcoma by inhibiting TCF7L1.
基金Supported by Ruian Natural Science Foundation,No.MS2021008.
文摘BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.
基金funded by National Key R&D Program of China(NO.2022YFD1300303)National Natural Science Foundation of China(32272849)。
文摘Background The proliferation of porcine ovarian granulosa cells(GCs)is essential to follicular development and the ubiquitin–proteasome system is necessary for maintaining cell cycle homeostasis.Previous studies found that the deubiquitinase ubiquitin carboxyl-terminal hydrolase 1(UCHL1)regulates female reproduction,especially in ovarian development.However,the mechanism by which UCHL1 regulates porcine GC proliferation remains unclear.Results UCHL1 overexpression promoted GC proliferation,and knockdown had the opposite effect.UCHL1 is directly bound to cyclin B1(CCNB1),prolonging the half-life of CCNB1 and inhibiting its degradation,thereby promoting GC proliferation.What's more,a flavonoid compound-isovitexin improved the enzyme activity of UCHL1 and promoted the proliferation of porcine GCs.Conclusions UCHL1 promoted the proliferation of porcine GCs by stabilizing CCNB1,and isovitexin enhanced the enzyme activity of UCHL1.These findings reveal the role of UCHL1 and the potential of isovitexin in regulating proliferation and provide insights into identifying molecular markers and nutrients that affect follicle development.
基金Shaanxi Province Natural Science Foundation,China(Grant No.:2021JM-568).
文摘Hyaluronan and proteoglycan link protein 1(Hapln1)supports active cardiomyogenesis in zebrafish hearts,but its regulation in mammal cardiomyocytes is unclear.This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell(hiPSC)-derived cardiomyocytes(CMs)and an adult mouse model of myocardial infarction.HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models,respectively.Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration.The results showed that recombinant human Hapln1(rhHapln1)promotes the proliferation of hiPSC-CMs in a dose-dependent manner.As a physical binding protein of Hapln1,versican interacted with Nodal growth differentiation factor(NODAL)and growth differentiation factor 11(GDF11).GDF11,but not NODAL,was expressed by hiPSC-CMs.GDF11 expression was unaffected by rhHapln1 treatment.However,this molecule was required for rhHapln1-mediated activation of the transforming growth factor(TGF)-β/Drosophila mothers against decapentaplegic protein(SMAD)2/3 signaling in hiPSC-CMs,which stimulates cell dedifferentiation and proliferation.Recombinant mouse Hapln1(rmHapln1)could induce cardiac regeneration in the adult mouse model of myocardial infarction.In addition,rmHapln1 induced hiPSC-CM proliferation.In conclusion,Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-β/SMAD2/3 signaling pathway.Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.
基金supported by the National Natural Science Foundation of China[Grant Number:81972803]。
文摘Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.
基金supported by the China Agriculture Research System of MOF and MARA。
文摘As a cell proliferation regulator involved in wide biological processes in plants,GRF-INTERACTING FACTOR(GIF)controls different tissues development.However,whether GIF participates in fruit development remains unclear.According to transcriptome data,we identified PbGIF1was highly expressed during fruit development in cytokinins induced parthenocarpy pear.In the present study,the biofunction of PbGIF1 was initially verified.Overexpression of PbGIF1 promoted fruit size of transgenic tomato.The size of flesh fruit was not affected by cell expansion but the cell proliferation was promoted by overexpressing Pb GIF1.The accelerated cell proliferation process was also observed in PbGIF1-overexpressed transgenic pear fruit calli.The transcriptional regulation of cytokinins on PbGIF1 was further confirmed by exogenous CPPU treatments in pear fruitlets.To investigate the underlying mechanism,the cytokinins-responded factor,PbRR1,was further focused on.The results of Yeast-one-hybrid assay suggested that PbRR1 can bind to the promoter sequence of PbGIF1.The transcriptional activation of PbRR1 on PbGIF1 was also confirmed by Dual-Luciferase assays.Taken together,the results showed that cytokinins control pear fruit development via the transcriptional activation of PbGIF1 by PbRR1.
