微小RNA-499（mieroRNA-499，miR-499）是近年来发现的肌球蛋白基因编码的miRNA（miRNA encoded by myosingene，myo—miR）家族新成员，目前发现它主要在人和动物的心肌和骨骼肌中表达，同时在其它多种组织中也可以被检测到。miR-499...微小RNA-499（mieroRNA-499，miR-499）是近年来发现的肌球蛋白基因编码的miRNA（miRNA encoded by myosingene，myo—miR）家族新成员，目前发现它主要在人和动物的心肌和骨骼肌中表达，同时在其它多种组织中也可以被检测到。miR-499在心肌细胞的分化中起着至关重要的调控作用。在成人心肌和骨骼肌中，miR-499通过促进β-肌球蛋白重链（β—myosin heavy chain，p-MHC）的表达，使肌细胞的氧代谢和耐受力增强。miR-499可能通过不同的信号转导通路，参与了不同的心肌病理过程。此外，miR-499的血清／血浆水平在多种疾病患者中有显著变化，miR-499前体（pre—miR-499）的多态性也与人体对多种疾病的易感性相关，这些使其有望成为某些疾病临床检验的生物学标志物之一。展开更多
Background:Abnormal expression of long non-coding RNAs(lncRNAs)has been found in almost all tumors in humans,providing numerous potential diagnostic and prognostic biomarkers,and therapeutic targets.Materials and meth...Background:Abnormal expression of long non-coding RNAs(lncRNAs)has been found in almost all tumors in humans,providing numerous potential diagnostic and prognostic biomarkers,and therapeutic targets.Materials and methods:The Cancer Genome Atlas(TCGA)database was used to screen potential LncRNAs,and 30 paired hepatocellular carcinoma(HCC)tissues were used to investigate RP11-307C12.11 expression levels by qRT-PCR and another 105 HCC tissues by in situ hybridizsation(ISH).RP11-307C12.11 overexpression and knockdown experiments were performed to investigate the effects of RP11-307C12.11 on HCC growth through in vitro and in vivo assays(MTT assay,colony formation assay,EdU assay,and xenograft model).The molecular mechanism underlying these effects was confirmed by MS2-RIP-assay,RIP assay,luciferase assay,and rescue experiments.Results:RP11-307C12.11 expression level was significantly higher in tumor tissues than in the adjacent normal tissues.Elevated RP11-307C12.11 expression level was associated with poor prognosis of HCC patients,and it may be represented as an independent prognostic biomarker in patients with HCC.Functionally,RP11-307C12.11 overexpression promoted HCC growth both in vitro and in vivo;however,its knockdown reversed these effects.Mechanistically,we found that RP11-307C12.11 expressed predominantly in the cytoplasm and sponged microRNA(miR)-138 to regulate its common target CCND1 and PDK1.Conclusions:Thus,we found that RP11-307C12.11 acts as an oncogene in HCC by binding to miR-138,which might provide a novel target for HCC therapy.展开更多
文摘微小RNA-499（mieroRNA-499，miR-499）是近年来发现的肌球蛋白基因编码的miRNA（miRNA encoded by myosingene，myo—miR）家族新成员，目前发现它主要在人和动物的心肌和骨骼肌中表达，同时在其它多种组织中也可以被检测到。miR-499在心肌细胞的分化中起着至关重要的调控作用。在成人心肌和骨骼肌中，miR-499通过促进β-肌球蛋白重链（β—myosin heavy chain，p-MHC）的表达，使肌细胞的氧代谢和耐受力增强。miR-499可能通过不同的信号转导通路，参与了不同的心肌病理过程。此外，miR-499的血清／血浆水平在多种疾病患者中有显著变化，miR-499前体（pre—miR-499）的多态性也与人体对多种疾病的易感性相关，这些使其有望成为某些疾病临床检验的生物学标志物之一。
基金supported by:the National Natural Science Foundation of China(81702393,81770648,81670601,81570593)Key Scientific and Technological Projects of Guangdong Province(2015B020226004,2017A020215178)+4 种基金Guangdong Natural Science Foundation(2017A030310373,2015A030312013)Science and Technology Planning Project of Guangdong Province(2017B030314027,2017B020209004,2015B020226004)Science and Technology Planning Project of Guangzhou(2014Y2e00544)Guangzhou Science and Technology Huimin Special Project(2014Y2e00200)Sun Yat-sen University Young Teacher Training Project(17ykpy47).
文摘Background:Abnormal expression of long non-coding RNAs(lncRNAs)has been found in almost all tumors in humans,providing numerous potential diagnostic and prognostic biomarkers,and therapeutic targets.Materials and methods:The Cancer Genome Atlas(TCGA)database was used to screen potential LncRNAs,and 30 paired hepatocellular carcinoma(HCC)tissues were used to investigate RP11-307C12.11 expression levels by qRT-PCR and another 105 HCC tissues by in situ hybridizsation(ISH).RP11-307C12.11 overexpression and knockdown experiments were performed to investigate the effects of RP11-307C12.11 on HCC growth through in vitro and in vivo assays(MTT assay,colony formation assay,EdU assay,and xenograft model).The molecular mechanism underlying these effects was confirmed by MS2-RIP-assay,RIP assay,luciferase assay,and rescue experiments.Results:RP11-307C12.11 expression level was significantly higher in tumor tissues than in the adjacent normal tissues.Elevated RP11-307C12.11 expression level was associated with poor prognosis of HCC patients,and it may be represented as an independent prognostic biomarker in patients with HCC.Functionally,RP11-307C12.11 overexpression promoted HCC growth both in vitro and in vivo;however,its knockdown reversed these effects.Mechanistically,we found that RP11-307C12.11 expressed predominantly in the cytoplasm and sponged microRNA(miR)-138 to regulate its common target CCND1 and PDK1.Conclusions:Thus,we found that RP11-307C12.11 acts as an oncogene in HCC by binding to miR-138,which might provide a novel target for HCC therapy.
