title: MicroRNA-761 is upregulated in hepatocellular carcinoma and regulates tumorigenesis by targeting Mitofusin-2.
abstract: Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-related deaths worldwide. The fate of a cell is determined by the balance between the processes of fission and fusion that constantly occur in the mitochondria of cells. We previously showed that overexpression of Mitofusin-2 can induce apoptosis in HCC cells by triggering an influx of Ca(2+) into the mitochondria from the ER. The function of Mitofusin-2 has been studied extensively, but the mechanism underlying the post-transcriptional regulation of Mitofusin-2 has not been elucidated. In the present study, we aimed to identify the mechanism of Mitofusin-2 regulation in HCC. We demonstrated that Mitofusin-2 is a direct target of miR-761, which was found to be upregulated in HCC tissues. Furthermore, a miR-761 inhibitor impaired mitochondrial function by upregulating Mitofusin-2 and effectively repressed tumor growth and metastasis both in vivo and in vitro. Our findings provide new insight into the mechanism underlying Mitofusin-2 regulation and the potential role of miR-761 in HCC, making it a potential candidate for use in HCC therapy in the future.
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Xiaohu
authors: X
authors: Zhou
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Linshi
authors: L
authors: Zhang
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Bichun
authors: B
authors: Zheng
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Yingcai
authors: Y
authors: Yan
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Yuan
authors: Y
authors: Zhang
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Haiyang
authors: H
authors: Xie
authors: Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
authors: Lin
authors: L
authors: Zhou
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Shusen
authors: S
authors: Zheng
authors: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
authors: Weilin
authors: W
authors: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D035683:MicroRNAs; D024101:Mitochondrial Proteins; C000610045:microRNA761 microRNA, human; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human
keywords: Cell proliferation; Mfn2; MiR-761; hepatocellular carcinoma; mitochondria