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ANGPTL4 Stabilizes Bone Morphogenetic Protein 7 Through Deubiquitination and Promotes HCC Proliferation via the

Yun Bai1, Guanghua Cui1, Xiaoke Sun1

  • 1Department of Oncology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

DNA and Cell Biology
|June 3, 2024
PubMed

Insights

Angiopoietin-related protein 4 (ANGPTL4) promotes hepatocellular carcinoma (HCC) by inhibiting BMP7 ubiquitination. Bone morphogenetic protein 7 (BMP7) overexpression reverses ANGPTL4

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) remains a significant global health challenge.
  • Understanding the molecular mechanisms driving HCC progression is crucial for developing effective therapies.
  • The roles of angiopoietin-related protein 4 (ANGPTL4) and bone morphogenetic protein 7 (BMP7) in HCC are not fully elucidated.

Purpose of the Study:

  • To investigate the functional interaction between ANGPTL4 and BMP7 in HCC.
  • To determine the mechanism by which ANGPTL4 influences BMP7 stability and signaling.
  • To explore the therapeutic potential of targeting the ANGPTL4-BMP7 axis in HCC.

Main Methods:

  • Co-transfection of HepG2 cells with ANGPTL4 and BMP7 overexpressing plasmids.
  • Assessment of ANGPTL4's effect on BMP7 expression and ubiquitination levels.
  • In vitro and in vivo experiments involving ANGPTL4 knockdown and BMP7 overexpression.
  • Analysis of downstream signaling pathways, including Smad1/5/8 and MAPK14.

Main Results:

  • ANGPTL4 directly interacts with BMP7.
  • Knockdown of ANGPTL4 leads to increased BMP7 expression and ubiquitination.
  • Overexpression of BMP7 counteracted the inhibitory effects of ANGPTL4 knockdown on HCC proliferation and migration.
  • ANGPTL4 knockdown reduced the expression of Smad1/5/8 and MAPK14, which was reversed by BMP7 overexpression.

Conclusions:

  • ANGPTL4 promotes HCC proliferation and migration by inhibiting BMP7 ubiquitination and degradation.
  • The ANGPTL4-BMP7 interaction impacts the Smad/MAPK signaling pathway.
  • Targeting the ANGPTL4-BMP7 axis offers a novel therapeutic strategy for HCC.
Keywords:
ANGPTL4BMP7MAPKhepatocellular carcinomaubiquitination

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