ZAG promotes colorectal cancer cell proliferation and epithelial-mesenchymal transition by promoting lipid synthesis.

Abstract

Colorectal cancer (CRC) is a common malignant tumor characterized by a high degree of invasiveness, and since zinc-α2 glycoprotein (ZAG) has been implicated in the progression of several malignancies, this study was designed to investigate the role of ZAG in CRC. Its expression was assessed using the GEPIA database, and short hairpin RNA (shRNA) interference was conducted to create ZAG knockdown in CRC cell lines. We also conducted lipid synthesis, cell proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) experiments to elucidate the effects of ZAG expression on CRC, as well as explored the potential underlying mechanistic pathways. Our findings reveal that ZAG is overexpressed in CRC. In vitro, ZAG knockdown resulted in the suppression of lipid production, cell division, and EMT while concurrently promoting apoptosis. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway was found to mediate the effects of ZAG on CRC cells. In conclusion, the downregulation of ZAG can inhibit CRC cell survival, EMT, and lipid production via the PI3K/AKT/mTOR signaling pathway.