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Acquisition of epithelial‐mesenchymal transition (EMT) has recently been proposed as an important contributor of drug resistance in cervical cancer cells. However, the underlying mechanisms are still unclear. MicroRNAs play a crucial role in regulating EMT. The aim of this study was to explore the potential role of miR‐25‐3p in regulating EMT in cisplatin‐resistant (CR) cervical cancer cells. To this end, we established stable CR cervical cancer cells, HeLa‐CR and CaSki‐CR, and investigated the function of miR‐25‐3p in regulating EMT. It is found that CR cervical cancer cells possessed more EMT characteristics and demonstrated higher migratory abilities and invasiveness. miR‐25‐3p downregulation was also seen in HeLa‐CR and CaSki‐CR cells. Of note, ectopic expression of miR‐25‐3p reversed the EMT phenotype and sensitized CR cells to cisplatin via targeting Sema4C. Furthermore, stable overexpression of miR‐25‐3p in HeLa‐CR cells suppressed tumor growth in mice, downregulated Sema4C and Snail, and upregulated E‐cadherin compared with the control group. These results suggest that miR‐25‐3p is an important regulator of cervical cancer EMT and chemoresistance. Thus, upregulation of miR‐25‐3p could be a novel approach to treat cervical cancers that are resistant to chemotherapy.

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