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

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.