The Akt/GSK3β/β-catenin signaling regulated by ZCCHC14 is responsible for accelerating the proliferation of hepatocellular carcinoma.

Purpose To clarify how ZCCHC14 affects the development of hepatocellular carcinoma (HCC). Methods Differential levels of ZCCHC14 in HCC tissues and cells were examined. Proliferative and migratory changes in HCC cells with overexpression or knockdown of ZCCHC14 were detected using 5-Ethynyl-2'- deoxyuridine (EdU) and Transwell assay, respectively. Expression changes of p-Akt/Akt, p-GSK3β/GSK3β and β-catenin in HCC cells mediated by ZCCHC14 were determined. Intervened by the p-Akt activator SC79 or overexpression of β-catenin, further validated the involvement of the Akt/GSK3β/β-catenin signaling in HCC cell phenotypes mediated by ZCCHC14. Results Upregulated ZCCHC14 in HCC accelerated in vitro proliferative potential of HCC cells. Knockdown of ZCCHC14 inactivated the Akt/GSK3β/β-catenin signaling and inhibited malignant phenotypes of HCC, which were partially reversed by SC79 induction or overexpression of β-catenin. Conclusions By activating the Akt/GSK3β/β-catenin signaling, ZCCHC14 accelerates HCC cells proliferation.