MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluste...MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis.It has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 cluster.Collectively,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 families.Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses.Various targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and metastasis.In this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory loop.In addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.展开更多
Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival rates.Extracellular vesicles,particularly exosomes,play a pivotal role in the formation and...Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival rates.Extracellular vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions.However,the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown.This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site.This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)expression.Addressing this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/215.These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic sites.Intervention with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing mice.These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.展开更多
Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the...Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.展开更多
MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, t...MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.展开更多
This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM)and the association with biomarkers of inflammation ...This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM)and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease(DKD).A total of 390 patients with T2DM were divided into three groups:normal albuminuria(UACR<30 mg/g,n=136,NA),microalbuminuria(UACR at 30-300 mg/g,n=132,MA),and clinical albuminuria(UACR>300 mg/g,n=122,CA).Circulating miR-154-5p,inflammatory(C-reactive protein(CRP);erythrocyte sedimentation rate(ESR);and tumor necrosis factor-a(TNF-α)and fibrotic markers(vascular endothelial growth factor(VEGF);transforming growth factor-β1(TGF-β1);and fibronectin(FN),and other biochemical indicators were assessed via real-time PCR,enzyme-linked immunosorbent assay,and chemiluminescence assay in patients with T2DM and 138 control subjects(NC).UACR,miR-154-5p,glycated hemoglobin(HbA1c),serum creatinine(sCr),blood urea nitrogen(BUN),ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were significantly higher and the estimated glomerular filtration rate(eGFR)was significantly lower in NA,MA,and CA groups than in NC subjects(P<0.05).Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c,sCr,BUN,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN and negatively correlated with eGFR(P<0.05).miR-154-5p,HbA1c,sCr,BUN,eGFR,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were important factors affecting UACR.These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.展开更多
文摘MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation.The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis.It has two other paralogs in the human genome,the miR-106b-25 cluster and the miR-106a-363 cluster.Collectively,the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families,namely the miR-17,the miR-92,the miR-18and the miR-19 families.Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma.Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses.Various targets of these microRNAs have been identified,and these targets are involved in tumor growth,cell survival and metastasis.In this review,we first describe the regulation of these clusters by c-Myc and E2F1,and how the members of these clusters inturn regulate E2F1 expression forming an auto-regulatory loop.In addition,the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.
基金This research received funding from the National Natural Science Foundation of China(Grant Nos.:82274073,82304713,and 81872986)was supported by the Jiangsu Provincial Excellent Postdoctoral Program(Grant Numbers:2022ZB291,China).
文摘Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival rates.Extracellular vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary lesions.However,the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely unknown.This study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor site.This transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)expression.Addressing this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/215.These nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic sites.Intervention with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing mice.These findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.
文摘Constitutive hedgehog （Hh） signaling is associated with the genesis of medulloblastomas （MB）. The objective of this study is to identify special microRNAs （miRNAs） regulated by the Hh pathway, and to clarify the role of miRNAs during the genesis of MB induced by sustained Hh activation. In the primary screening, we used stemloop RT-PCR to test the expression of 90 different miRNAs in the wildtype （WT） and Ptc-/- MEF cell lines. In the secondary screening, the miRNAs screened from the first screening were validated in the Sufu-/- MEF cell lines. We then verified the expression of miRNAs both in the normal cerebellar tissues and the MB induced by activated Hh pathway, and examined the expression of the other 21 miRNA members of the miR-154 cluster in the MB and normal cerebellum. In the first screening, 13 miRNAs showed significant differential expression in WT and Ptc-/- MEF cell lines, while 10 of them had significant difference in the Sufu-/- MEF cell line. Compared to the normal mouse cerebellum, only 2 miRNAs in 15 miRNAs were differentially expressed between the MB and normal cerebellar tissues. Among 21 members of the miR-154 cluster, 6 miRNAs were downregulated in the MB. Our study demonstrated that miR-154 may be regulated by the Hh pathway, and the activation of the Hh pathway led to the downregulation of the miR-154 cluster, resulting in the genesis of MB.
文摘MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.
基金This study was supported by the Higher School“High-end Talent Team Construction”of Liaoning Province(No.[2014]187)the Natural Science Foundation of Liaoning Province(No.201602862),Liaoning Province,China.
文摘This study aimed to investigate the correlation between serum miR-154-5p and urinary albumin to creatinine ratio(UACR)in patients with type 2 diabetes mellitus(T2DM)and the association with biomarkers of inflammation and fibrosis in diabetic kidney disease(DKD).A total of 390 patients with T2DM were divided into three groups:normal albuminuria(UACR<30 mg/g,n=136,NA),microalbuminuria(UACR at 30-300 mg/g,n=132,MA),and clinical albuminuria(UACR>300 mg/g,n=122,CA).Circulating miR-154-5p,inflammatory(C-reactive protein(CRP);erythrocyte sedimentation rate(ESR);and tumor necrosis factor-a(TNF-α)and fibrotic markers(vascular endothelial growth factor(VEGF);transforming growth factor-β1(TGF-β1);and fibronectin(FN),and other biochemical indicators were assessed via real-time PCR,enzyme-linked immunosorbent assay,and chemiluminescence assay in patients with T2DM and 138 control subjects(NC).UACR,miR-154-5p,glycated hemoglobin(HbA1c),serum creatinine(sCr),blood urea nitrogen(BUN),ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were significantly higher and the estimated glomerular filtration rate(eGFR)was significantly lower in NA,MA,and CA groups than in NC subjects(P<0.05).Elevated levels of UACR and miR-154-5p were directly correlated with HbA1c,sCr,BUN,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN and negatively correlated with eGFR(P<0.05).miR-154-5p,HbA1c,sCr,BUN,eGFR,ESR,CRP,VEGF,TNF-α,TGF-β1,and FN were important factors affecting UACR.These findings indicated that elevated serum miR-154-5p is significantly correlated with high UACR in patients with T2DM and may offer a novel reference for the early diagnosis of DKD.
