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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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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DOI: https://doi.org/10.1038/cgt.2017.6
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