Overexpression of microRNA-195-5p reduces cisplatin resistance and angiogenesis in ovarian cancer by inhibiting the PSAT1-dependent GSK3β/β-catenin signaling pathway

Abstract

Background: Ovarian cancer (OC) is one of the leading causes for cancer-related deaths among women. MicroRNAs (miRs) have been proved to be vital to the development and progression of OC. Hence, the study aims to evaluate the ability of miR-195-5p affecting cisplatin (DDP) resistance and angiogenesis in OC and the underlying mechanism. Methods: MiRs that could target phosphoserine aminotransferase 1 (PSAT1), a differentially expressed gene in OC, were predicted by miRNA-mRNA prediction websites. The expression patterns of miR-195-5p in the OC tissues and cells were determined using RNA quantification assay. The role of miR-195-5p in OC was evaluated by determining DDP resistance, apoptosis and angiogenesis of OC cells after up-regulating or down-regulating miR-195-5p or PSAT1, or blocking the glycogen synthase kinase-3β (GSK3β)/β-catenin signaling pathway. Animal experiment was conducted to explore the effect of miR-195-5p on resistance to DDP and angiogenesis. Result: MiR-195-5p directly targeted PSAT1 and down-regulated its expression. The expression of miR-195-5p was lower while that of PSAT1 was higher in OC tissues than in adjacent normal tissues. When miR-195-5p was over-expressed or PSAT1 was silenced, the expression of HIF-1α, VEGF, PSAT1, β-catenin as well as the extent of GSK3β phosphorylation was reduced, the angiogenesis and resistance to DDP was diminished and apoptosis was promoted both in vitro and in vivo. The inhibition of GSK3β/β-catenin signaling pathway was involved in the regulation process. Conclusion: Over-expression of miR-195-5p reduced angiogenesis and DDP resistance in OC, which provides a potential therapeutic target for the treatment of OC.