PRPF overexpression induces drug resistance through actin cytoskeleton rearrangement and epithelial-mesenchymal transition

Abstract

Pre-mRNA processing factor (PRPF) 4B kinase belongs to the CDK-like kinase family, and is involved in pre-mRNA splicing, and in signal transduction. In this study, we observed that PRPF overexpression decreased the intracellular levels of reactive oxygen species, and inhibited resveratrol-induced apoptosis by activating the cell survival signaling proteins NFκB, ERK, and c-MYC in HCT116 human colon cancer cells. PRPF overexpression altered cellular morphology, and rearranged the actin cytoskeleton, by regulating the activity of Rho family proteins. Moreover, it decreased the activity of RhoA, but increased the expression of Rac1. In addition, PRPF triggered the epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116, PC3 human prostate, and B16-F10 melanoma cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRPF. Taken together, these results indicate that PRPF blocks the apoptotic effects of resveratrol by activating cell survival signaling pathways, rearranging the actin cytoskeleton, and inducing EMT. The elucidation of the mechanisms that underlie anticancer drug resistance and the anti-apoptosis effect of PRPF may provide a therapeutic basis for inhibiting tumor growth and preventing metastasis in various cancers.