title: The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for hepatocyte apoptosis and hepatocarcinogenesis.
abstract: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with an increasing incidence worldwide. Apolipoprotein M (apoM) is a novel apolipoprotein that is mainly expressed in liver and kidney tissues. However, the anti-tumor properties of apoM remain largely unknown. We evaluated the anti-tumor activities and mechanisms of apoM in HCC both in vivo and in vitro. Bioinformatic analysis and luciferase reporter assay results showed that apoM was a potential target of hsa-miR-573 and was downregulated after transfection with hsa-miR-573 mimics. Overexpression of apoM suppressed migration, invasion, and proliferation of hepatoma cells in vitro. Overexpression of hsa-miR-573 in hepatoma cells reduced apoM expression, leading to promotion of the invasion, migration, and proliferation of hepatoma cells in vitro. In addition, hsa-miR-573 markedly promoted growth of xenograft tumors in nude mice with an accompanying reduction in cell apoptosis. ApoM markedly inhibited growth of xenograft tumors in nude mice and promoted cell apoptosis. Moreover, Bcl2A1 mRNA and protein levels were inhibited by apoM overexpression and an increase in apoptosis rate by apoM was markedly compensated by Bcl2A1 overexpression in HepG2 cells. These results provide evidence that hsa-miR-573 promoted tumor growth by inhibition of hepatocyte apoptosis and this pro-tumor effect might be mediated through Bcl2A1 in an apoM-dependent manner. Therefore, our findings may be useful to improve understanding of the critical effects of hsa-miR-573 and apoM in HCC pathogenesis.
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Chen
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Hu
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zhao
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Li
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Qiu
authors.forename: Xiao-Juan
authors.initials: XJ
authors.lastname: Wu
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Sha
authors.forename: Ji-Juan
authors.initials: JJ
authors.lastname: Gao
authors.forename: Yan-Chao
authors.initials: YC
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism; D000075243:Apolipoproteins M; D017209:Apoptosis; D063646:Carcinogenesis / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D020413:3' Untranslated Regions; C400523:APOM protein, human; D001053:Apolipoproteins; D000075243:Apolipoproteins M; C096816:BCL2-related protein A1; D054834:Lipocalins; C585063:MIRN573 microRNA, human; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2