iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling

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 in cc samples and associated with poor prognosis in cc patients. conclusions: iaspp promotes emt and confers cisplatin resistance in cc via mir-20a-fbxl5/btg3 signaling. © 2017 the author(s).