title: Pro-apoptotic and anti-proliferative effects of mitofusin-2 via Bax signaling in hepatocellular carcinoma cells.
abstract: Mitochondrial GTPase mitofusin-2 (Mfn2) is a novel gene that remarkably suppresses the injury-mediated proliferation of vascular smooth muscle cells (VSMCs) and has a potential apoptotic effect via the mitochondrial apoptotic pathway. Hepatocellular carcinoma (HCC) tissues and matched normal tissues were examined for mfn2 expression. HCC cells were infected with adenovirus carrying Mfn2 (Ad-mfn2) or green fluorescent protein (Ad-GFP), used as a control. Short hairpin RNA (shRNA) was formed by shR-mfn2 and shR-Bax to repress mfn2 and Bax transcription, respectively. The effects of mfn2 on cell cycle distribution and apoptosis were measured by flow cytometric analysis. Significant downregulation of mfn2 was observed in HCC tissues compared with nearby normal tissues. Overexpression of mfn2 inhibited HCC cell proliferation and induced apoptosis by increasing the level of active caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. Overexpression of mfn2 also induced cytochrome c release to the cytoplasm by enhancing Bax translocation from the cytoplasm to the mitochondrial membrane. Upregulation of mfn2 promoted apoptosis of HCC cells, and this was dramatically suppressed by shR-Bax. Our results show that the mfn2 gene is a potential tumor suppressor target that may significantly promote apoptosis via Bax and may inhibit proliferation in HCC cells. This gene may be an important therapeutic target for the treatment of tumors or hyperproliferative diseases.
authors.affiliation: Key Lab of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, People's Republic of China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Wang
authors.forename: Jianju
authors.initials: J
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wei
authors.forename: Changku
authors.initials: C
authors.lastname: Jia
authors.forename: Yuanbiao
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation; D005434:Flow Cytometry; D020558:GTP Phosphohydrolases / Q000235:genetics* / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering; D015398:Signal Transduction; D014162:Transfection; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human