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  • Original Article
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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.

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Acknowledgements

This work was supported by Primary Research and Development Plan of Shandong Province (2015GSF118140); National Natural Science Foundation of China Emergency Management Project (81441075); Natural Science Foundation of Shandong Province (ZR2014HM108 and ZR2013HQ030).

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Correspondence to Y Tian.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Liu, Y., Niu, Z., Lin, X. et al. MiR-216b increases cisplatin sensitivity in ovarian cancer cells by targeting PARP1. Cancer Gene Ther 24, 208–214 (2017). https://doi.org/10.1038/cgt.2017.6

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