Mir-454-3p induced WTX deficiency promotes hepatocellular carcinoma progressions through regulating TGF-β signaling pathway

Hui Liu^1#, Juan Zheng^2#, Shengqian Yang^1#, Qibei Zong¹, Zhiwen Wang³, Xinghua Liao^1✉

1. Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Hubei, 430081, P. R. China.
2. Department of Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Shandong, 252000, P. R. China.
3. Yueyang Key Laboratory of Chronic Noncommunicable Diseases, Yueyang Vocational & Technical College, Hunan, 414000, P. R. China.
#These authors contributed equally to this work.

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Citation:
Liu H, Zheng J, Yang S, Zong Q, Wang Z, Liao X. Mir-454-3p induced WTX deficiency promotes hepatocellular carcinoma progressions through regulating TGF-β signaling pathway. J Cancer 2022; 13(6):1820-1829. doi:10.7150/jca.67478. Available from https://www.jcancer.org/v13p1820.htm

Abstract

Background: Wilms tumor gene on X chromosome (WTX) is an X-linked tumor suppressor gene in Wilms tumor; however, however, the molecular mechanism of WTX in the occurrence and development of HCC has not been reported.

Methods: The expression of miR-454-3p and WTX wre analyzed in 32 matched human HCC and normal tissue samples. The molecular mechanisms of miR-454-3p/WTX/TGFβ signaling in cell proliferation, migration, invasion and autophagy were investigated in vitro and in vivo.

Results: WTX expression was downregulated in HCC tissues; lower WTX levels were associated with poor HCC patient outcomes. WTX loss triggers the activation of TGF-β signaling, which promotes HCC cells proliferation, migration, invasion and autophagy. Further mechanistic study showed that the aberrant upregulation of miR-454-3p was identified as the reason of WTX loss in HCC.

Conclusions: WTX is a tumor suppressor gene in HCC, miR-454-3p/WTX/TGFβ signaling will provide a new direction for the diagnosis and treatment of HCC.

Keywords: miR-454-3p, WTX, HCC, metastasis, autophagy