期刊
ONCOGENESIS
卷 5, 期 -, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/oncsis.2016.1
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资金
- General Program of 309th Hospital of PLA [2015MS-010]
- National Natural Science Foundation [81472589, 31100604]
- Beijing Nova Program [Z141102001814055]
Cervical cancer ( CC) is one of the most common malignancies in women. Paclitaxel is the front-line chemotherapeutic agent for treating CC. However, its therapeutic efficacy is limited because of chemoresistance, the mechanism of which remains poorly understood. Here, we used microRNA ( miRNA) arrays to compare miRNA expression levels in the CC cell lines, HeLa and CaSki, with their paclitaxel resistance counterparts, HeLa/PR and CaSki/PR. We demonstrate that miR-125a was one of most significantly downregulated miRNAs in paclitaxel-resistant cells, which also acquired cisplatin resistance. And that the upregulation of miR-125a sensitized HeLa/PR and CaSki/PR cells to paclitaxel both in vitro and in vivo and to cisplatin in vitro. Moreover, we determined that miR-125a increased paclitaxel and cisplatin sensitivity by downregulating STAT3. MiR-125a enhanced paclitaxel and cisplatin sensitivity by promoting chemotherapy-induced apoptosis. Clinically, miR-125a expression was associated with an increased responsiveness to paclitaxel combined with cisplatin and a more favorable outcome. These data indicate that miR-125a may be a useful method to enable treatment of chemoresistant CC and may also provide a biomarker for predicting paclitaxel and cisplatin responsiveness in CC.
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