title: miR-25-3p reverses epithelial-mesenchymal transition via targeting Sema4C in cisplatin-resistance cervical cancer cells.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, The Fourth Clinical Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Gynecology, The Hospital of Heilongjiang Province, Nangang Branch, Harbin, Heilongjiang, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D039961:Semaphorins / Q000235:genetics*; D000071250:Snail Family Transcription Factors / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; C000592635:Sema4c protein, human; D039961:Semaphorins; D000071250:Snail Family Transcription Factors; D002945:Cisplatin
keywords: Cervical cancer; cisplatin; drug resistance; epithelial-mesenchymal transition; miR-25-3p