Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells

Abstract

Sema4C, the target of many miRNAs, is involved in EMT-mediated chemotherapeutic resistance of many malignant tumors. However, the underlying upstream regulatory mechanisms of Sema4C-induced EMT and Sema4C-mediated drug resistance are still unclear. The aim of this study was to explore the potential role of miR-31-3p/Sema4C in regulating EMT in cisplatin-resistant (CR) cervical cancer cells. High expression levels of Sema4C were more frequently found in cervical cancer tissues and were associated with poor prognosis, whereas miR-31-3p was significantly downregulated in cervical cancer tissues, which was associated with shorter disease-free and overall survival. Overexpression of miR-31-3p inhibited malignant behaviors and EMT of cervical cancer cells in vitro. Furthermore, miR-31-3p was identified to directly target Sema4C, and upregulation of miR-31-3p reversed EMT-mediated biological functions, including cisplatin resistance of Sema4C in cervical cancer cells. These results suggest that Sema4C promoted EMT-mediated cisplatin resistance in cervical cancer cells and that this effect was inhibited by overexpression of miR-31-3p. Thus, silencing Sema4C or overexpression of miR-31-3p could be a novel approach to treat drug resistance to chemotherapy in cervical cancers.