MiR-216b increases cisplatin sensitivity in ovarian cancer cells by targeting PARP1

Abstract

Cisplatin resistance hinders the efficacy of chemotherapy in ovarian cancer. MicroRNAs (miRs) have been implicated in drug resistance in anti-cancer chemotherapy. We compared the expression profiles of miRs between cisplatin-resistant and cisplatin-sensitive ovarian cancer cells, and found that miR-216b was significantly downregulated in cisplatin-resistant ovarian cancer cells. To investigate its molecular mechanism, we performed cell viability and apoptosis assays in cisplatin-resistant ovarian cells, and found that miR-216b reduced cell viability and promoted apoptosis. Although 4 potential targets were obtained through bioinformatics, only the mRNA level of poly(ADP-ribose) polymerase (PARP)-1 was significantly regulated by miR-216b. Disruption of the complementary binding sequence of miR-216b on the 3'-untranslated region (3'-UTR) of the PARP1 led to the loss of miR-216b targeting. Spearman's correlation coefficient of the levels of miR-216b and PARP1 mRNA from 51 human ovarian cancer specimens also showed a significantly negative correlation between them. Importantly, the improved cisplatin sensitivity induced by miR-216b was markedly reversed by PARP1 overexpression. Tumor formation assay in nude mice further provided an evidence on the suppressive role of miR-216b in tumor growth. Taken together, this study demonstrated that a new miRNA, miR-216b, was involved in cisplatin resistance in ovarian cancer, which could be regarded as a potential sensitizer in cisplatin chemotherapy.

Long non‐coding RNA Linc00518 promotes paclitaxel resistance of the human prostate cancer by sequestering miR‐216b‐5p

“…Intriguingly, there were two reports uncovered the potential link between miR‐216b with drug resistance. The first one demonstrated that miR‐216b enhanced the efficacy of vemurafenib by targeting Beclin‐1, UARAG and ATG5 in melanoma [Luo et al., ], while the second one proposed that miR‐216b increased cisplatin sensitivity in ovarian cancer cells by targeting PARP1 [Liu et al., ]. Consistent with the latter study, here we characterised the competitive down‐regulation of miR‐216b by Linc00518, which subsequently contributed to the paclitaxel resistance via releasing the suppression over GATA6.…”

<p>MiR-935 Promotes Clear Cell Renal Cell Carcinoma Migration and Invasion by Targeting IREB2</p>

“…It is reported that miRNA is involved in tumorigenesis, acting variously as either oncogenes [24][25][26][27] or tumor suppressors. 16,28,29 Increasing evidence has demonstrated that miRNAs are effective biomarkers and tumor regulators in kidney cancer and therefore have broad implications in both clinical and therapeutic practice.…”

Crosstalk between the lncRNA UCA1 and microRNAs in cancer

“…In addition, UCA1 also conferred cisplatin resistance in ovarian cancer through up-regulation of serine/arginine-rich protein-specific kinase 1 [11], a target of miR-216b [117][118][119]. Consistently, miR-216b increases cisplatin sensitivity in ovarian cancer cells [120] and could be sponged by UCA1 [34]. Furthermore, UCA1 could sponge miR-129 to enhance resistance to paclitaxel, which is used for chemotherapeutic treatment of many cancers including ovarian cancer [121].…”