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

Yiran Chen; Xiaoling Wu; Xi Chen; Deliang Guo; Weijie Ma; Yonghua Guo; Kequan Xu; Shuxian Ma; Yufeng Yuan; Qian Zhu

doi:10.2147/JHC.S404008

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. eCollection 2023.

Authors

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.

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.

Grants and funding

This work was supported by the National Natural Science Foundation of China (82002589), Grant from the Key Research and Development Program of Hubei Province (2021BCA114), Research Fund of the Health Commission of Hubei Province (WJ2021M255), Cancer research and translational platform project of Zhongnan Hospital of Wuhan University (ZLYNXM202004).