目的本研究旨在阐明miR-150在肝细胞癌(hepatocellular carcinoma,HCC)中的作用和靶点。方法采用热图分析方法,从癌症基因组图谱(The Cancer Genome Atlas)数据库下载的6组HCC组织与邻近肝组织之间差异表达的miRNA。采用实时定量聚合酶...目的本研究旨在阐明miR-150在肝细胞癌(hepatocellular carcinoma,HCC)中的作用和靶点。方法采用热图分析方法,从癌症基因组图谱(The Cancer Genome Atlas)数据库下载的6组HCC组织与邻近肝组织之间差异表达的miRNA。采用实时定量聚合酶链反应检测miR-150在HCC组织和细胞系中的表达;采用侵袭小室试验评估HCC细胞的增殖、侵袭和迁移潜能。此外,利用TargetScan软件用于预测miR-150的潜在靶标,并通过蛋白印迹(Western blotting)和荧光素酶法测定miR-150与其靶基因的关系。结果通过热图分析法,发现在HCC组织中有31个miRNA表达异常,其中miR-150表达差异最为显著,且与患者预后密切相关。细胞实验上,高表达miR-150可通过调节胰岛素样生长因子2-mRNA结合蛋白2(recombinant insulin like growth factor 2 mRNA binding protein 2,IGF2BP2)的表达显著降低人肝癌细胞株SMMC-7721和HepG2细胞的增殖、迁移和侵袭能力。结论miR-150通过调控IGF2BP2抑制HCC细胞的增殖、迁移和侵袭,为HCC提供了新的治疗靶点。展开更多
Background The association between IGF2BP2 and type 2 diabetes mellitus （T2DM） has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies （GWAS） from the ...Background The association between IGF2BP2 and type 2 diabetes mellitus （T2DM） has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies （GWAS） from the Chinese Han population, the gene IGF2BP2 has not been replicated. The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population. It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.展开更多
Accumulating evidence indicates that RNA methylation at N6-methyladenosine(m6A)plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers.How...Accumulating evidence indicates that RNA methylation at N6-methyladenosine(m6A)plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers.However,little is known whether and how m6A-modification impacts long non-coding RNA(lncRNA)and lncRNA-mediated tumorigenesis,particularly in pancreatic ductal adenocarcinoma(PDAC).In the present study,we report that a previously uncharacterized lncRNA,LINC00901,promotes pancreatic cancer cell growth and invasion and moreover,LINC00901 is subject to m6A modification which regulates its expression.In this regard,YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level.Notably,two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1.Finally,RNA sequencing(RNA-seq)and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2,a known RNA binding protein that can enhance MYC mRNA stability.Together,our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.展开更多
Circular RNAs(circRNAs)are playing emerging role in the pathogenesis of cancers,but the mechanisms still unknown.In the recent issue of the Nature Communications,Chen and colleagues have demonstrated that YTHDC1 facil...Circular RNAs(circRNAs)are playing emerging role in the pathogenesis of cancers,but the mechanisms still unknown.In the recent issue of the Nature Communications,Chen and colleagues have demonstrated that YTHDC1 facilitates N6-methyladenosine modified circNSUN2 cytoplasmic export and the circNSUN2/IGF2BP2/HMGA2 complex stabilizes HMGA2 to promote colorectal liver metastasis.These discoveries not only expand our understanding of circRNAs biology in tumor,but also demonstrate that m6A modification plays a key role for circRNAs in RNA metabolism.Therefore,these findings indicate that circRNAs may be a new approach for therapeutic target of cancers.展开更多
Nonalcoholic steatohepatitis(NASH)has emerged as the major cause of end-stage liver diseases.However,an incomplete understanding of its molecular mechanisms severely dampens the development of pharmacotherapies.In the...Nonalcoholic steatohepatitis(NASH)has emerged as the major cause of end-stage liver diseases.However,an incomplete understanding of its molecular mechanisms severely dampens the development of pharmacotherapies.In the present study,through systematic screening of genome-wide mRNA expression from three mouse models of hepatic inflammation and fibrosis,we identified IGF2BP2,an N6-methyladenosine modification reader,as a key regulator that promotes NASH progression in mice.Adenovirus or adeno-associated virus-mediated overexpression of IGF2BP2 could induce liver steatosis,inflammation,and fibrosis in mice,at least in part,by increasing Tab2 mRNA stability.Besides,hepatic overexpression of IGF2BP2 mimicked gene expression profiles and molecular pathways of human NASH livers.Of potential clinical significance,IGF2BP2 expression is significantly upregulated in the livers of NASH patients.Moreover,knockdown of IGF2BP2 substantially alleviated liver injury,inflammation,and fibrosis in diet-induced NASH mice.Taken together,our findings reveal an important role of IGF2BP2 in NASH,which may provide a new therapeutic target for the treatment of NASH.展开更多
文摘目的本研究旨在阐明miR-150在肝细胞癌(hepatocellular carcinoma,HCC)中的作用和靶点。方法采用热图分析方法,从癌症基因组图谱(The Cancer Genome Atlas)数据库下载的6组HCC组织与邻近肝组织之间差异表达的miRNA。采用实时定量聚合酶链反应检测miR-150在HCC组织和细胞系中的表达;采用侵袭小室试验评估HCC细胞的增殖、侵袭和迁移潜能。此外,利用TargetScan软件用于预测miR-150的潜在靶标,并通过蛋白印迹(Western blotting)和荧光素酶法测定miR-150与其靶基因的关系。结果通过热图分析法,发现在HCC组织中有31个miRNA表达异常,其中miR-150表达差异最为显著,且与患者预后密切相关。细胞实验上,高表达miR-150可通过调节胰岛素样生长因子2-mRNA结合蛋白2(recombinant insulin like growth factor 2 mRNA binding protein 2,IGF2BP2)的表达显著降低人肝癌细胞株SMMC-7721和HepG2细胞的增殖、迁移和侵袭能力。结论miR-150通过调控IGF2BP2抑制HCC细胞的增殖、迁移和侵袭,为HCC提供了新的治疗靶点。
文摘Background The association between IGF2BP2 and type 2 diabetes mellitus （T2DM） has been repeatedly confirmed among different ethnic populations. However, in several genome-wide association studies （GWAS） from the Chinese Han population, the gene IGF2BP2 has not been replicated. The results of relevant studies for the association between IGF2BP2 and T2DM showed controversy in Chinese Han population. It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population.
基金supported by grants from National Natural Science Foundation of China(No.82072703 to WP,No.81772575 and No.81972455 to LY)US Department of Defense(No.CA170314 to YM).
文摘Accumulating evidence indicates that RNA methylation at N6-methyladenosine(m6A)plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers.However,little is known whether and how m6A-modification impacts long non-coding RNA(lncRNA)and lncRNA-mediated tumorigenesis,particularly in pancreatic ductal adenocarcinoma(PDAC).In the present study,we report that a previously uncharacterized lncRNA,LINC00901,promotes pancreatic cancer cell growth and invasion and moreover,LINC00901 is subject to m6A modification which regulates its expression.In this regard,YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level.Notably,two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1.Finally,RNA sequencing(RNA-seq)and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2,a known RNA binding protein that can enhance MYC mRNA stability.Together,our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.
基金Natural Science Foundation of China(81773165)Hunan Province Science Fund for Distinguished Young Scholars(2018JJ1021)+1 种基金the Key R&D Program of Hunan Province(2017SK2172)the Science and Technique Foundation of Chenzhou(jsyf2017023).
文摘Circular RNAs(circRNAs)are playing emerging role in the pathogenesis of cancers,but the mechanisms still unknown.In the recent issue of the Nature Communications,Chen and colleagues have demonstrated that YTHDC1 facilitates N6-methyladenosine modified circNSUN2 cytoplasmic export and the circNSUN2/IGF2BP2/HMGA2 complex stabilizes HMGA2 to promote colorectal liver metastasis.These discoveries not only expand our understanding of circRNAs biology in tumor,but also demonstrate that m6A modification plays a key role for circRNAs in RNA metabolism.Therefore,these findings indicate that circRNAs may be a new approach for therapeutic target of cancers.
基金This study was supported by the National Key Research and Development Program of China(2018YFA0800402)the Shanghai Outstanding Academic Leaders Projects(21XD1423400)+3 种基金the Basic Research of Science,and Technology Innovation Action Plan(21JC1401300)Shanghai Sailing Program by Shanghai Municipal Science and Technology Committee(22YF1432800)China Postdoctoral Science Foundation Funded Project(2021M702183)the Youth Cultivation Project of Shanghai Jiao Tong University Affiliated Sixth People’s Hospital(ynqn202107).
文摘Nonalcoholic steatohepatitis(NASH)has emerged as the major cause of end-stage liver diseases.However,an incomplete understanding of its molecular mechanisms severely dampens the development of pharmacotherapies.In the present study,through systematic screening of genome-wide mRNA expression from three mouse models of hepatic inflammation and fibrosis,we identified IGF2BP2,an N6-methyladenosine modification reader,as a key regulator that promotes NASH progression in mice.Adenovirus or adeno-associated virus-mediated overexpression of IGF2BP2 could induce liver steatosis,inflammation,and fibrosis in mice,at least in part,by increasing Tab2 mRNA stability.Besides,hepatic overexpression of IGF2BP2 mimicked gene expression profiles and molecular pathways of human NASH livers.Of potential clinical significance,IGF2BP2 expression is significantly upregulated in the livers of NASH patients.Moreover,knockdown of IGF2BP2 substantially alleviated liver injury,inflammation,and fibrosis in diet-induced NASH mice.Taken together,our findings reveal an important role of IGF2BP2 in NASH,which may provide a new therapeutic target for the treatment of NASH.
