Abstract 4378: miR-100 mediates resistance to paclitaxel in cervical cancer cells

Abstract

Abstract Objectives: Hypoxia occurs during development of cervical cancer and is considered to correlate with its resistance to chemotherapy. We found that hypoxia induced miR-100 whose expression was low in cervical cancer. We sought to determine the regulators of the paclitaxel response during hypoxia in cervical cancer. Methods and Results: We found that the expression of miR-100 was significantly higher under hypoxic condition (1% O2) by realtime RT-PCR. According to the results of in silico analysis, miR-100 targeted human ubiquitin-specific protease (USP) 15. Hypoxia and overexpression of miR-100 respectively decreased the activity of luciferase-reporter containing the 3′-untranslated region (UTR) of USP15 with the predicted miR-100-binding site in cervical cancer cell lines, SiHa and HeLa. By western blot analysis, hypoxia enhanced the endogenous USP15 protein expression. USP15 mRNA level was also up-regulated by hypoxia using realtime RT-PCR. Overexpression of miR-100 induced paclitaxel resistance reducing apoptosis using MTT assays and annexin V staining. Conclusions: Our results provide evidence that regulation of USP15 expression by miR-100 represents a mechanism for paclitaxel resistance in cervical cancer. Our results suggest that miR-100 and USP15 could be a therapeutic target in paclitaxel-resistant cervical cancer. Citation Format: Rina Kato, Hirotaka Nishi, Yuzo Nagamitsu, Toru Sasaki, Keiichi Isaka. miR-100 mediates resistance to paclitaxel in cervical cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4378. doi:10.1158/1538-7445.AM2014-4378