Wnt8B, transcriptionally regulated by ZNF191, promotes cell proliferation of hepatocellular carcinoma via Wnt signaling.

Dysregulation of wingless-type (Wnt) signaling has been implicated in hepatocellular carcinoma (HCC). Wnt8B, one of canonical Wnt ligands, has been implicated in oncogenesis. However, the role of Wnt8B in human HCCs and its transcriptional regulation mechanism remain unknown presently. Here we report that Wnt8B expression was frequently increased in HCCs, and was significantly associated with poorer patient prognosis. Wnt8B knockdown suppresses HCC cell growth both in vitro and in vivo, via inhibiting canonical Wnt signaling. Transcription factor ZNF191 can positively regulate Wnt8B mRNA and proteins expression, and promoter luciferase assay indicated that ZNF191 can increase transcription activity of 2Kbps WNT8B promoter. Chromatin immunoprecipitation- qPCR and Electrophoretic mobility shift assay showed ZNF191 protein directly binds to WNT8B promoter and the binding sites are at nt-1491(ATTAATT) and nt-1178(ATTCATT). Moreover, Wnt8B contributes the effect of ZNF191 on cell proliferation, and Wnt8B expression correlates positively with ZNF191 in human HCCs. Our findings suggested that Wnt8B, directly transcriptionally regulated by ZNF191, plays a pivotal role in HCC proliferation via canonical Wnt pathway, and may serve as a new prognostic biomarker and a potential therapeutic target for HCC patients.