LncRNA TGFB2-OT1 Promotes Progression and Angiogenesis in Hepatocellular Carcinoma by Dephosphorylating β-Catenin

  • J Hepatocell Carcinoma. 2023 Mar 14;10:429-446. doi: 10.2147/JHC.S404008.
Yiran Chen  #  1  2 ,  Xiaoling Wu  #  3 ,  Xi Chen  1  2 ,  Deliang Guo  1  2 ,  Weijie Ma  1  2 ,  Yonghua Guo  1  2 ,  Kequan Xu  1  2 ,  Shuxian Ma  1  2 ,  Yufeng Yuan  1  2  4 ,  Qian Zhu  1  2
Affiliations
  • 1. Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, 430071, People's Republic of China.
  • 2. Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, People's Republic of China.
  • 3. Department of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
  • 4. TaiKang Center for Life and Medical Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.
  • # Contributed equally.
PMID: 36941998 DOI: 10.2147/JHC.S404008
Abstract

Introduction: Hepatocellular carcinoma (HCC) was the sixth most prevalent Cancer worldwide. Long non-coding RNA TGFB2-OT1 has been proven to mediate inflammation and Autophagy in vascular endothelial cells. However, its function in HCC is still unknown.

Methods: We analyzed the relationship between TGFB2-OT1 expression and the clinicopathological features of 202 HCC patients. RT-qPCR was used to analyze the TGFB2-OT1 expression in HCC cell lines and tissues. In vitro and in vivo assays were conducted to verify the effect of TGFB2-OT1 on the phenotype of HCC. RNA pull-down assays were applied to reveal the proteins binding to the TGFB2-OT1. Western-blot assays were conducted to analyze the protein expression in HCC cell lines.

Results: TGFB2-OT1 was found to be highly expressed in HCC samples and hepatoma cells. TGFB2-OT1 expression was significantly associated with age (P = 0.001), cirrhosis (P = 0.003), tumor size (P < 0.001), tumor encapsulation (P = 0.029), tumor protruding from the liver surface (P = 0.040), and alpha fetoprotein (AFP, P < 0.001) levels. TGFB2-OT1 promoted proliferation, migration, invasion, and angiogenesis in HCC cells, both in vitro and in vivo. TGFB2-OT1 binds to β-catenin and competitively impaired the binding of β-catenin to GSK3β, thus suppressing the phosphorylation of β-catenin at Ser33, Ser37, and Thr41.

Conclusion: TGFB2-OT1 is overexpressed in HCC and predicts the poor prognosis of HCC patients. TGFB2-OT1 impedes the phosphorylation of β-catenin and acts as an alternative activator of the Wnt/β-catenin pathway to promote the progression and angiogenesis of HCC.

Keywords
HCC; TGFB2-OT1; angiogenesis; phosphorylation; β-catenin.
Products
Inhibitors & Agonists
Other Products