The miR-573/apoM/Bcl2A1-dependent signal transduction pathway is essential for hepatocyte apoptosis and hepatocarcinogenesis

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• 作者：Yan-Wei Hu ; Zhi-Ping Chen ; Xiu-Mei Hu ; Jia-Yi Zhao ; Jin-Lan Huang ; Xin Ma…
• 关键词：HCC ; miR ; 573 ; apoM ; Bcl2A1 ; Apoptosis
• 刊名：Apoptosis
• 出版年：2015
• 出版时间：October 2015
• 年：2015
• 卷：20
• 期：10
• 页码：1321-1337
• 全文大小：7,589 KB
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• 作者单位：Yan-Wei Hu (1)
  Zhi-Ping Chen (1)
  Xiu-Mei Hu (1)
  Jia-Yi Zhao (1)
  Jin-Lan Huang (1)
  Xin Ma (2)
  Shu-Fen Li (1)
  Yu-Rong Qiu (1)
  Xiao-Juan Wu (1)
  Yan-Hua Sha (1)
  Ji-Juan Gao (1)
  Yan-Chao Wang (1)
  Lei Zheng (1)
  Qian Wang (1)
  
  1. Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
  2. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
  
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Cell Biology
  Biochemistry
  Virology
  
• 出版者：Springer Netherlands
• ISSN：1573-675X

文摘

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. Keywords HCC miR-573 apoM Bcl2A1 Apoptosis