Abstract
WD‑repeat domain phosphoinositide‑interacting protein 2 (WIPI2) is a protein that regulates the assembly of multiprotein complexes by presenting a beta‑propeller platform for simultaneous and reversible protein‑protein interactions. This study was designed to investigate the association between the expression of WIPI2 and the growth of hepatocellular carcinoma (HCC). Publicly‑available data from the UALCAN platform revealed that WIPI2 is upregulated in tumor tissues compared with that noted in normal tissues in many types of tumors especially in HCC, and high WIPI2 expression predicts a poor patient prognosis. WIPI2 expression was significantly higher in tumor tissues compared with that in the corresponding adjacent normal tissues. Depletion of WIPI2 inhibited the proliferation and promoted the apoptosis both in HCC Huh7 and Hep3B cells. In order to explore the mechanisms of WIPI2 in HCC, WIPI2 was depleted in HCC cell lines and a gene microarray was constructed. The bioinformatic analysis showed that WIPI2 regulated the proliferation of HCC cells mainly through the AMPK signaling pathway. Further analysis indicated that the downstream factors of the AMPK signaling pathway were downregulated after WIPI2 depletion. Collectively, our study revealed that WIPI2 plays an important role in the pathogenesis of HCC mainly through the AMPK signaling pathway.