Over-expression of miR-31 or loss of KCNMA1 leads to increased cisplatin resistance in ovarian cancer cells

Abstract

Ovarian cancers have a high mortality rate; this is in part due to resistance to the platinum-based compounds used in chemotherapy. In this paper, we assess the role of microRNA-31 in the development of chemoresistance to cisplatin. We used previous data from microarray experiments to identify potential microRNAs (miRNAs) involved in chemoresistance. The functional significance of these microRNAs was tested using miRNA mimics. We used RNA-seq to identify pathways and genes de-regulated in the resistant cell line and then determined their role using RNAi. Analysis of publically available datasets reveals the potential clinical significance. Our data show that miR-31 is increased, whilst potassium channel calcium activated large conductance subfamily M alpha, member 1 (KCNMA1), a subunit of calcium-regulated big potassium (BK) channels, is reduced in resistant ovarian cells. Over-expression of miR-31 increased resistance, as did knockdown of KCNMA1 or inhibition of BK channels. This suggests that these genes directly modulate cisplatin response. Our data also suggest that miR-31 represses KCNMA1 expression. Comparing the levels of miR-31 and KCNMA1 to cisplatin resistance in the NCI60 panel or chemoresistance in cohorts of ovarian cancer tumours reveals correlations that support a role for these genes in vitro and in vivo. Here we show that miR-31 and KCNMA1 are involved in mediating cisplatin resistance in ovarian cancer. Our data gives a new insight into the potential mechanisms to therapeutically target in cisplatin resistance common to ovarian cancer.

MicroRNA-20a contributes to cisplatin-resistance and migration of OVCAR3 ovarian cancer cell line

“…Certain miRs may improve chemotherapy sensitivity, whereas others may induce chemoresistance of cancer cells (24)(25)(26). In ovarian cancer, miR-130a and miR-374a were demonstrated to function as negative regulators of cisplatin resistance in A2780 cells (27), whereas miR-31 positively regulated cisplatin resistance in numerous ovarian cancer cells (28). In the present study, miR-20a was identified as a novel positive regulator for OVCAR3 cells cisplatin resistance and migration.…”

Comprehensive analysis of lncRNA expression profiles reveals a novel lncRNA signature to discriminate nonequivalent outcomes in patients with ovarian cancer

“…Glycosylphosphatidylinositol (GPI) anchor is an unique type of glycoconjugate, and abnormal expression levels of certain components in the GPI-anchor biosynthetic pathway have been reported to be associated with various cancers [74]. A recent experimental study provided evidence for the role of calcium-related genes in mediating cisplatin resistance in ovarian cancer cells [75]. Taken together, these analyses suggested that the eight prognostic lncRNAs might have important biologic relevance in regulating or interacting PCGs involved in OvCa, but further experimentally validation is required.…”

MiR-31 regulates the cisplatin resistance by targeting Src in gallbladder cancer

“…MiR-31 is not only linked to tumor proliferation, invasion and metastasis, but also to the acquisition of onco-chemoresistance [10]. Wang et al showed that suppression of miR-31 increased sensitivity to 5-FU and inhibited cell migration and invasion in colon cancer [18].…”