Suppression of c-FLIPL promotes JNK activation in malignant melanoma cells

Abstract

The up-regulation of cellular Fas-associated death domain-like interleukin-1β-converting enzyme (FLICE)-like inhibitory protein (c-FLIP) has been reported in various tumor types, and has been previously shown to be associated with the clinicopathological features of melanoma. To assess its potential role in cancer therapy, the present study evaluated the effects of short hairpin (sh)RNAs of different c-FLIP isoforms on cellular proliferation and c-Jun N-terminal kinase (JNK) signaling. Human c-FLIP shRNA plasmids were constructed and transfected into the A875 melanoma cell line. It was observed that c-FLIP shRNA exhibited strong inhibitory effects against the levels of phosphorylated-JNK and inhibited cellular proliferation in A875 cells. Thus, this indicated that c-FLIP long form shRNA serves a specific inhibitory role in cellular proliferation through inducing the activation of the JNK pathway in A875 cells. The present study provided insight into the development of RNAi based therapies for melanoma.