Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation o...Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation of malignant tumor cells.Fra-1 is highly expressed in gastric cancer(GC),affects the cycle distribution and apoptosis of GC cells,and participates in GC occurrence and development.However,the detailed mechanism of Fra-1 in GC is unclear,such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis.In this study,we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta(YWHAH)as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry.Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression,and affected GC cell proliferation.Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1(HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway in GC cells.Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation.These results will help to discover new molecular targets for the early diagnosis,treatment,and prognosis prediction of GC.展开更多
Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal.It produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to s...Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal.It produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to sustain normal cellular functions.Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions,including pro-grammed cell death.Ferroptosis is a recently discovered form of iron-dependent programmed cell death.The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression.However,the role of cellular metabolism,particularly glucose and amino acid metabolism,in cancer ferroptosis is not well understood.Here,we reviewed glucose,lipid,amino acid,iron and sele-nium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process.Additionally,we provided a detailed overview of agents used to induce cancer ferroptosis.We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellu-lar redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death,resulting in enhanced tumor cell killing.The combination of ferroptosis inducers and cel-lular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.展开更多
Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor c...Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.展开更多
Cancer is one of the leading causes of human death worldwide.Treatment of cancer exhausts significant medical resources,and the morbidity and mortality caused by cancer is a huge social burden.Cancer has therefore bec...Cancer is one of the leading causes of human death worldwide.Treatment of cancer exhausts significant medical resources,and the morbidity and mortality caused by cancer is a huge social burden.Cancer has therefore become a serious economic and social problem shared globally.As an increasingly prevalent disease in China,cancer is a huge challenge for the country’s healthcare system.Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality in China in 2016,we analyzed the current trends in cancer incidence and changes in cancer mortality and survival rate in China.And also,we examined several key risk factors for cancer pathogenesis and discussed potential countermeasures for cancer prevention and treatment in China.展开更多
Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a pre...Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis.Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells,resulting in diverse biological consequences including decreased lipolysis,immune regulation,and anti-inflammation wound healing,and enhanced exercise performance in association with the gut microbiome.Furthermore,increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones,which accounts for its key role in immune modulation and maintenance of homeostasis.Here,we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.展开更多
A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes i...A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics,which is called metabolite sensing.Life body regulates metabolism,immunity,and inflammation by metabolite sensing,coordinating the pathophysiology of the host to achieve balance with the external environment.Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell,including cell proliferation,migration,invasion,angiogenesis,etc.Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer,thus forming a vicious circle.At the same time,exogenous metabolites can also affect the biological behavior of tumors.Here,we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives,as well as their abnormalities in the development of various cancers,and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.展开更多
Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the preci...Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in mammals.The m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic processes.Intriguingly,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor development.In this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis pathways.We also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.展开更多
Glycosylation,a key mode of protein modification in living organisms,is critical in regulating various biological functions by influencing protein folding,transportation,and localization.Changes in glycosylation patte...Glycosylation,a key mode of protein modification in living organisms,is critical in regulating various biological functions by influencing protein folding,transportation,and localization.Changes in glycosylation patterns are a significant feature of cancer,are associated with a range of pathological activities in cancer-related processes,and serve as critical biomarkers providing new targets for cancer diagnosis and treatment.Glycoproteins like human epidermal growth factor receptor 2(HER2)for breast cancer,alpha-fetoprotein(AFP)for liver cancer,carcinoembryonic antigen(CEA)for colon cancer,and prostatespecific antigen(PSA)for prostate cancer are all tumor biomarkers approved for clinical use.Here,we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA(glycoRNA).This article focuses primarily on tumor metastasis,immune evasion,metabolic reprogramming,aberrant ferroptosis responses,and cellular senescence to illustrate the role of glycosylation in cancer.Additionally,we summarize the clinical applications of protein glycosylation in cancer diagnostics,treatment,and multidrug resistance.We envision a promising future for the clinical applications of protein glycosylation.展开更多
Cancer is a major threat to human health and causes death worldwide.Research on the role of radiotherapy(RT)in the treatment of cancer is progressing;however,RT not only causes fatal DNA damage to tumor cells,but also...Cancer is a major threat to human health and causes death worldwide.Research on the role of radiotherapy(RT)in the treatment of cancer is progressing;however,RT not only causes fatal DNA damage to tumor cells,but also affects the interactions between tumor cells and different components of the tumor microenvironment(TME),including immune cells,fibroblasts,macrophages,extracellular matrix,and some soluble products.Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME.Currently,the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood.This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.展开更多
Actin filament associated protein 1 antisense RNA 1(named AFAP1-AS1)is a long non-coding RNA and overexpressed in many cancers.This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer.The AFAP1-...Actin filament associated protein 1 antisense RNA 1(named AFAP1-AS1)is a long non-coding RNA and overexpressed in many cancers.This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer.The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization.The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells.To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer,we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses.AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients'poor prognosis.In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis.AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1(named SNIP1),which inhibited ubiquitination and degradation of c-Myc protein.Upregulation of c-Myc molecule in turn promoted the expression of ZEB1,ZEB2,and SNAIL gene,which ultimately enhanced epithelial to mesenchymal transition(EMT)and lung cancer metastasis.Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients'early diagnosis and therapy.展开更多
Aryl hydrocarbon receptor(AHR)was considered to be an important pan-tumor therapeutic target,but small molecule inhibitors targeting AHR target gene ID01 have failed in clinical trials.The recent paper published in Ce...Aryl hydrocarbon receptor(AHR)was considered to be an important pan-tumor therapeutic target,but small molecule inhibitors targeting AHR target gene ID01 have failed in clinical trials.The recent paper published in Cell by Opitz et al.explained the failure of previous clinical trials and identified new therapeutic targets(Fig.1).展开更多
Long non-coding RNAs(lncRNAs)have become a hotspot in biomedical research.This interest reflects their extensive involvement in the regulation of the expression of other genes,and their influence on the occurrence and...Long non-coding RNAs(lncRNAs)have become a hotspot in biomedical research.This interest reflects their extensive involvement in the regulation of the expression of other genes,and their influence on the occurrence and development of a variety of human diseases.Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1)is a recently discovered oncogenic lncRNA.It is highly expressed in a variety of solid tumors,and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs,or by the direct binding to other proteins.Ultimately,AFAP1-AS1 promotes proliferation,chemotherapy resistance,and resistance to apoptosis,maintains stemness,and enhances invasion and migration of tumor cells.This paper summarizes the research concerning AFAP1-AS1 in malignant tumors,including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors.We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research.AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.展开更多
基金This work was supported by the Hunan Provincial Natural Science Foundation(2021JJ30915).
文摘Fos-related antigen 1(Fra-1)is a nuclear transcription factor that regulates cell growth,differentiation,and apoptosis.It is involved in the proliferation,invasion,apoptosis and epithelial mesenchymal transformation of malignant tumor cells.Fra-1 is highly expressed in gastric cancer(GC),affects the cycle distribution and apoptosis of GC cells,and participates in GC occurrence and development.However,the detailed mechanism of Fra-1 in GC is unclear,such as the identification of Fra-1-interacting proteins and their role in GC pathogenesis.In this study,we identified tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein eta(YWHAH)as a Fra-1-interacting protein in GC cells using co-immunoprecipitation combined with liquid chromatography-tandem mass spectrometry.Experiments showed that YWHAH positively regulated Fra-1 mRNA and protein expression,and affected GC cell proliferation.Whole proteome analysis showed that Fra-1 affected the activity of the high mobility group AT-hook 1(HMGA1)/phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)/protein kinase B(AKT)/mechanistic target of rapamycin(mTOR)signaling pathway in GC cells.Western blotting and flow cytometry confirmed that YWHAH activated HMGA1/PI3K/AKT/mTOR signaling pathway by positively regulating Fra-1 to affect GC cell proliferation.These results will help to discover new molecular targets for the early diagnosis,treatment,and prognosis prediction of GC.
基金This work was sup-ported in part by grants from the following sources:the National Natural Science Foundation of China(82203233,82202966,82173142,82302987,82303534,and 81972636)the Natural Science Foundation of Hunan Province(2023JJ60469,2023JJ40413,2023JJ30372,2023JJ30375,2022JJ80078,and 2020JJ5336)+8 种基金the Research Project of Health Commission of Hunan Province(202203034978,202109031837,and 20201020)Key Research and Devel-opment Program of Hunan Province(2022SK2051)Hunan Provincial Science and Technology Department(2020TP1018)the Changsha Science and Technology Board(kh2201054)the Changsha Municipal Natural Science Foundation(kq2014209)Ascend Foundation of National Cancer Center(NCC201909B06)Hunan Cancer Hospital Climb Plan(ZX2020001-3 and YF2020002)the Science and Technology Innovation Program of Hunan Province(2023RC3199,2023SK4034 and 2023RC1073)by China Postdoctoral Science Foundation(2022TQ0104 and 2022M721118).
文摘Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal.It produces energy,furnishes raw materials,and intermedi-ates for biomolecule synthesis,and modulates enzyme activity to sustain normal cellular functions.Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions,including pro-grammed cell death.Ferroptosis is a recently discovered form of iron-dependent programmed cell death.The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression.However,the role of cellular metabolism,particularly glucose and amino acid metabolism,in cancer ferroptosis is not well understood.Here,we reviewed glucose,lipid,amino acid,iron and sele-nium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process.Additionally,we provided a detailed overview of agents used to induce cancer ferroptosis.We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellu-lar redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death,resulting in enhanced tumor cell killing.The combination of ferroptosis inducers and cel-lular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.
基金supported by the National Natural Science Foundation of China(82203163)the Natural Science Foundation of Hunan Province(2022JJ40660)+1 种基金the Natural Science Foundation of Changsha(kq2202123)the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)。
文摘Adhesion molecules mediate cell-to-cell and cell-to-extracellular matrix interactions and transmit mechanical and chemical signals among them.Various mechanisms deregulate adhesion molecules in cancer,enabling tumor cells to proliferate without restraint,invade through tissue boundaries,escape from immune surveillance,and survive in the tumor microenvironment.Recent studies have revealed that adhesion molecules also drive angiogenesis,reshape metabolism,and are involved in stem cell self-renewal.In this review,we summarize the functions and mechanisms of adhesion molecules in cancer and the tumor microenvironment,as well as the therapeutic strategies targeting adhesion molecules.These studies have implications for furthering our understanding of adhesion molecules in cancer and providing a paradigm for exploring novel therapeutic approaches.
基金supported by the National Natural Science Foundation of China(U21A20382,U20A20367,82072374)the Overseas Expertise Introduction Project for Discipline Innovation(BP1221008)the Natural Science Foundation of Hunan Province(2021JJ30897,2021JJ41043).
文摘Cancer is one of the leading causes of human death worldwide.Treatment of cancer exhausts significant medical resources,and the morbidity and mortality caused by cancer is a huge social burden.Cancer has therefore become a serious economic and social problem shared globally.As an increasingly prevalent disease in China,cancer is a huge challenge for the country’s healthcare system.Based on recent data published in the Journal of the National Cancer Center on cancer incidence and mortality in China in 2016,we analyzed the current trends in cancer incidence and changes in cancer mortality and survival rate in China.And also,we examined several key risk factors for cancer pathogenesis and discussed potential countermeasures for cancer prevention and treatment in China.
基金supported by the National Natural Science Foundation of China(No.82060042)Guangxi Natural ScienceFoundation(China)(No.2020GXNSFBA297082)+1 种基金Guangxi Science and Technology Program Project(China)(No.AD19245005)The Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi(China)(No.2020KY12017).
文摘Lactate is an end product of glycolysis.Owing to the lactate shuttle concept introduced in the early 1980s,increasing researchers indicate lactate as a critical energy source for mitochondrial respiration and as a precursor of gluconeogenesis.Lactate also acts as a multifunctional signaling molecule through receptors expressed in various cells,resulting in diverse biological consequences including decreased lipolysis,immune regulation,and anti-inflammation wound healing,and enhanced exercise performance in association with the gut microbiome.Furthermore,increasing evidence reveals that lactate contributes to epigenetic gene regulation by lactylating lysine residues of histones,which accounts for its key role in immune modulation and maintenance of homeostasis.Here,we summarize the function and mechanism of lactate and lactylation in tumor metabolism and microenvironment.
基金supported by the National Natural Science Foundation of China[82072594(Y.T.),81874139,82073097(S.L.),81772496,82073136(D.X.)]Hunan Provincial Key Area R&D Programs[2019SK2253,2021SK2013,Y.T.]the Central South University Research Programme of Advanced Interdisciplinary Studies[2023QYJC030(Y.T.)].
文摘A wide spectrum of metabolites(mainly,the three major nutrients and their derivatives)can be sensed by specific sensors,then trigger a series of signal transduction pathways and affect the expression levels of genes in epigenetics,which is called metabolite sensing.Life body regulates metabolism,immunity,and inflammation by metabolite sensing,coordinating the pathophysiology of the host to achieve balance with the external environment.Metabolic reprogramming in cancers cause different phenotypic characteristics of cancer cell from normal cell,including cell proliferation,migration,invasion,angiogenesis,etc.Metabolic disorders in cancer cells further create a microenvironment including many kinds of oncometabolites that are conducive to the growth of cancer,thus forming a vicious circle.At the same time,exogenous metabolites can also affect the biological behavior of tumors.Here,we discuss the metabolite sensing mechanisms of the three major nutrients and their derivatives,as well as their abnormalities in the development of various cancers,and discuss the potential therapeutic targets based on metabolite-sensing signaling pathways to prevent the progression of cancer.
基金supported by the National Natural Science Foundation of China(82172592)the Free Exploration Program of Central South University(2021zzts0934)the program of Introducing Talents of Discipline to Universities(111-2-12)。
文摘Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in mammals.The m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic processes.Intriguingly,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor development.In this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis pathways.We also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.
基金supported in part by grants from the following sources:the National Natural Science Foundation of China(82472882,82302987,82303534,82203233,82202966,82173142)the Natural Science Foundation of Hunan Province(2024JJ4025,2023ZJ1122,Z2023086,2023JJ60469,2023JJ40413,2023JJ30372,2023JJ30375,2022JJ80078,2020JJ5336)+5 种基金Key Research and Development Program of Hunan Province(2022SK2051)Science and Technology Innovation Program of Hunan Province(2023RC3199,2023SK4034,2023RC1073)the Research Project of Health Commission of Hunan Province(R2023040,R2023093,202203034978,202202055318,202109031837,202109032010,20201020)the Changsha Science and Technology Board(kh2201054)Ascend Foundation of National cancer center(NCC201909B06)by Hunan Cancer Hospital Climb Plan(ZX2020001-3,YF2020002,2023NSFC-A001,2023NSFC-A002,2023NSFC-A004).
文摘Glycosylation,a key mode of protein modification in living organisms,is critical in regulating various biological functions by influencing protein folding,transportation,and localization.Changes in glycosylation patterns are a significant feature of cancer,are associated with a range of pathological activities in cancer-related processes,and serve as critical biomarkers providing new targets for cancer diagnosis and treatment.Glycoproteins like human epidermal growth factor receptor 2(HER2)for breast cancer,alpha-fetoprotein(AFP)for liver cancer,carcinoembryonic antigen(CEA)for colon cancer,and prostatespecific antigen(PSA)for prostate cancer are all tumor biomarkers approved for clinical use.Here,we introduce the diversity of glycosylation structures and newly discovered glycosylation substrate—glycosylated RNA(glycoRNA).This article focuses primarily on tumor metastasis,immune evasion,metabolic reprogramming,aberrant ferroptosis responses,and cellular senescence to illustrate the role of glycosylation in cancer.Additionally,we summarize the clinical applications of protein glycosylation in cancer diagnostics,treatment,and multidrug resistance.We envision a promising future for the clinical applications of protein glycosylation.
基金supported by the National Natural Science Foundation of China(No.82072594 to YT,Nos.82073097 and 81874139 to SL)Natural Science Foundation of Hunan Province,and Hunan Provincial Key Area Research&Development Programs(No.2021SK2013 to YT)
文摘Cancer is a major threat to human health and causes death worldwide.Research on the role of radiotherapy(RT)in the treatment of cancer is progressing;however,RT not only causes fatal DNA damage to tumor cells,but also affects the interactions between tumor cells and different components of the tumor microenvironment(TME),including immune cells,fibroblasts,macrophages,extracellular matrix,and some soluble products.Some cancer cells can survive radiation and have shown strong resistance to radiation through interaction with the TME.Currently,the complex relationships between the tumor cells and cellular components that play major roles in various TMEs are poorly understood.This review explores the relationship between RT and cell-cell communication in the TME from the perspective of immunity and hypoxia and aims to identify new RT biomarkers and treatment methods in lung cancer to improve the current status of unstable RT effect and provide a theoretical basis for further lung cancer RT sensitization research in the future.
基金This study was funded by the National Natural Science Foundation of China(82073135,81903015 and 81772928)the Overseas Expertise Introduction Project for Discipline Innovation(111 Project,No.111-2-12)the Natural Science Foundation of Hunan Province(20191)50780 and 2019JJ50872).
文摘Actin filament associated protein 1 antisense RNA 1(named AFAP1-AS1)is a long non-coding RNA and overexpressed in many cancers.This study aimed to identify the role and mechanism of AFAP1-AS1 in lung cancer.The AFAP1-AS1 expression was firstly assessed in 187 paraffin-embedded lung cancer and 36 normal lung epithelial tissues by in situ hybridization.The migration and invasion abilities of AFAP1-AS1 were investigated in lung cancer cells.To uncover the molecular mechanism about AFAP1-AS1 function in lung cancer,we screened proteins that interact with AFAP1-AS1 by RNA pull down and the mass spectrometry analyses.AFAP1-AS1 was highly expressed in lung cancer clinical tissues and its expression was positively correlated with lung cancer patients'poor prognosis.In vivo experiments confirmed that AFAP1-AS1 could promote lung cancer metastasis.AFAP1-AS1 promoted lung cancer cells migration and invasion through interacting with Smad nuclear interacting protein 1(named SNIP1),which inhibited ubiquitination and degradation of c-Myc protein.Upregulation of c-Myc molecule in turn promoted the expression of ZEB1,ZEB2,and SNAIL gene,which ultimately enhanced epithelial to mesenchymal transition(EMT)and lung cancer metastasis.Understanding the molecular mechanism by which AFAP1-AS1 promotes lung cancer's migration and invasion may provide novel therapeutic targets for lung cancer patients'early diagnosis and therapy.
基金This work was supported by the National Natural Science Foundation of China[81672787,82072594,Y.T.,81972638,W.L.,82002916,C.M.]China Postdoctoral Science Foundation[2019M652804,CM.]+4 种基金Natural Science Foundation of Hunan Province[2020JJ5790,C.M.]Hunan Provincial Key Area R&D Programs[2019SK2253,Y.T.]Postdoctoral Foundation of Central South University[220372,C.M.]Shenzhen Science and Technology Program[KQTD20170810160226082]Shenzhen Municipal Government of China[JCYJ20180507184647104].
文摘Aryl hydrocarbon receptor(AHR)was considered to be an important pan-tumor therapeutic target,but small molecule inhibitors targeting AHR target gene ID01 have failed in clinical trials.The recent paper published in Cell by Opitz et al.explained the failure of previous clinical trials and identified new therapeutic targets(Fig.1).
基金supported partially by grants from the National Natural Science Foundation of China(82073135,82072374,82003243,81903138,81803025)the Natural Science Foundation of Hunan Province(2019JJ50872,2020JJ4766).
文摘Long non-coding RNAs(lncRNAs)have become a hotspot in biomedical research.This interest reflects their extensive involvement in the regulation of the expression of other genes,and their influence on the occurrence and development of a variety of human diseases.Actin filament associated protein 1-Antisense RNA 1(AFAP1-AS1)is a recently discovered oncogenic lncRNA.It is highly expressed in a variety of solid tumors,and regulates the expression of downstream genes and signaling pathways through adsorption and competing microRNAs,or by the direct binding to other proteins.Ultimately,AFAP1-AS1 promotes proliferation,chemotherapy resistance,and resistance to apoptosis,maintains stemness,and enhances invasion and migration of tumor cells.This paper summarizes the research concerning AFAP1-AS1 in malignant tumors,including the clinical application prospects of AFAP1-AS1 as a potential molecular marker and therapeutic target of malignant tumors.We also discuss the limitations in the knowledge of AFAP1-AS1 and directions of further research.AFAP1-AS1 is expected to provide an example for studies of other lncRNA molecules.
