Pyrroline-5-carboxylate reductase 1 promotes cell proliferation via inhibiting apoptosis in human malignant melanoma.

Abstract

IntroductionHuman malignant melanoma (MM) is a highly malignant tumor of cutaneous melanocytes with a fast progression. We investigated the cellular effects of pyrroline-5- carboxylate reductase 1 (PYCR1) in the MM cell lines, A375 and M14.MethodsCell Counting Kit-8 assay, transwell assay, and flow cytometry analysis were performed to evaluate the proliferation, migration and apoptosis of MM cell lines, respectively. To gain more insight into the role of PYCR1 in tumor growth, we analyzed the AKT phosphorylation level in PYCR1-specific siRNA (siPYCR1) and negative control (NC) cells.ResultsBiochemical analysis revealed a clear increase in PYCR1 expression in human MM samples, and its high expression predicted a poor prognosis. Silencing of PYCR1 suppressed the proliferation and migration of A375 and M14 cells. The percentage of apoptosis in cells transfected with siPYCR1 significantly increased in comparison to that of cells transfected with negative control siRNA (NC). The enhanced apoptosis in PYCR1 knockdown cells was consistent with an increased level of markers of apoptosis. siPYCR1 inhibited AKT phosphorylation, as well as the expression of its downstream protein, P70, suggesting that PYCR1 promoted cell growth of the MM cell lines A375 and M14 through stimulation of the AKT pathway. Moreover, forkhead box K2 and regulatory associated protein of MTOR complex 1 shared a similar expression pattern to that of PYCR1 and were significantly downregulated in PYCR1 knockdown cells.ConclusionPYCR1 promoted tumor progression through the AKT pathway in human MM in vitro. Our results expand the knowledge of PYCR1 functions in solid tumors and provide a potential target for the clinical treatment of human MM.