2. Academic Validation
  3. RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression

RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression

  • Pharmacol Res. 2022 Dec 7;187:106593. doi: 10.1016/j.phrs.2022.106593.
Hexu Han 1,  Ting Lin 2,  Zhenyu Wang 3,  Jingjing Song 4,  Ziyi Fang 5,  Jing Zhang 5,  Xiaomin You 5,  Yanping Du 1,  Jun Ye 6,  Guoxiong Zhou 7
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu 225300, China.
  • 2 Department of Pathophysiology, School of Medicine, Nantong University, Jiangsu 226001, China.
  • 3 Department of pediatric surgery, Affiliated Hospital of Nantong University, Nantong University, Jiangsu 226001, China.
  • 4 Department of Pediatrics, the Second Affiliated Hospital &Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027 Zhejiang, China.
  • 5 Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Jiangsu 226001, China.
  • 6 Center for Translational Medicine, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu 225300, China. Electronic address: m13625171902@163.com.
  • 7 Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Jiangsu 226001, China. Electronic address: zhougx@ntu.edu.cn.
PMID: 36496136 DOI: 10.1016/j.phrs.2022.106593
Abstract

Increased angiogenesis in the liver plays a critical role in the progression of hepatocellular carcinoma (HCC). However, the molecular mechanism underlying increased angiogenesis in HCC is not well understood. Current study was designed to identify the potential angiogenic effect of RNA-binding motif 4 (RBM4)through a small-scale overexpression screening, followed by comparison of the expression level of RBM4 in Cancer and adjacent tissues in multiple malignancies to explore the relationship between RBM4 and CD31 protein expression level and related clinical indicators, and understand the role of RBM4 in the hepatocellular carcinoma. To understand the specific mechanism of RBM4 in detail, transcriptome Sequencing, mass spectrometry and multiple molecular cytological studies were performed. These cellular level results were verified by experiments in animal models of nude mice. The increased expression of RBM4 in Cancer tissues, suggested its use as a prognostic biomarker. The RBM4 expression was found to be strongly correlated with tumor microvessel density. Mechanistically, RBM4 mediated its effects via interaction with HNRNP-M through the latter's WDR15 domain, which then stabilized RelA/p65 mRNA. Consequently, RBM4 induced the activation of the NF-kB signaling pathway, upregulating the expression of proangiogenic factor VEGF-A. The results confirmed the mechanism by which RBM4 promotes angiogenesis in hepatocellular carcinoma suggesting RBM4 as a crucial promoter of angiogenesis in HCC, helping understand regulation of NF-kB signaling in HCC.

Keywords

Metastasis; NF-kappa B; Neovascularization; Prognosis; RBM4; p65.

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