子宫颈癌 顺铂学习.pdf

Xiong et al. Journal of Experimental Clinical Cancer Research (2017) 36:48 DOI 10.1186/s13046-017-0520-6 RESEARCH Open Access iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a- FBXL5/BTG3 signaling 1*† 2† 3* 4* 5,6* 7 1 Ying Xiong , Fei Sun , Peixin Dong , Hidemichi Watari , Junming Yue , Min-fei Yu , Chun-yan Lan , Yin Wang1 and Ze-biao Ma1 Abstract Background: Epithelial–mesenchymal transition (EMT) and dysregulated microRNAs (miRNAs) have important roles in driving chemoresistance. We previously reported that iASPP is a key EMT inducer and could increase cisplatin resistance in cervical cancer (CC) cells. Herein, we investigate the downstream mechanisms through which iASPP contributes to EMT and cisplatin resistance in CC. Methods: By using a lentiviral system, we investigated the effects of iASPP knockdown on CC cell growth and chemosensitivity of CC cells to cisplatin in vivo. We examined if miR-20a, which was up-regulated following iASPP overexpression, would influence metastatic phenotypes and cisplatin resistance in CC cells, and explored the possible molecular mechanisms involved. Results: Knockdown of iASPP suppressed CC cell proliferation and sensitized CC cells to cisplatin in vivo. iASPP promotes miR-20a expression in a p53-dependent manner. Upregulation of miR-20a induced EMT and the recovery of CC cell invasion and cisplatin chemoresistance that was repressed by iASPP knockdown. We identified FBXL5 and BTG3 as two direct miR-20a targets. Silencing of FBXL5 and BTG3 restored cell invasion and cisplatin chemoresistance, which was suppressed by iASPP or miR-20a knockdown. Reduced FBXL5 and BTG3 expression was found