PRMT5 Promotes Human Lung Cancer Cell Apoptosis via Akt/Gsk3β SignalingInduced by Resveratrol

摘要

Protein arginine methyltransferase 5 (PRMT5) is implicated in various types of humancancer and tumor development, especially in lung cancer. Nevertheless, it is still unclearwhether suppression of PRMT5 could promote lung cancer cell apoptosis and chemosensitivityinduced by resveratrol, and the underlying molecular mechanism remains completely unknown.Here, we showed that PRMT5 was overexpressed in human lung cancer tissues and differenttypes of lung cancer cell lines. Moreover, we constructed PRMT5 stable knockdown celllines (A549 and ASCT-a-1) and investigated the roles of PRMT5 and the related signalingpathway in lung cancer cell apoptosis induced by resveratrol. Our results indicated thatinhibition or down-regulation of PRMT5 by GSK591, a PRMT5-specific inhibitor, or shRNAsmarkedly enhanced cell apoptosis and chemosensitivity stimulated by resveratrol. Furtherinvestigation showed that inhibition or down-regulation of PRMT5 further reduced Akt/GSK3βphosphorylation and the downstream targets cyclin D1 and E1 expression upon resveratroltreatment. Our findings suggest that PRMT5 is a pivotal mediator for human lung cancercell death induced by resveratrol, which also reveals that PRMT5 may serve as a newtherapeutic target for the treatment of human lung cancer.