title: miR-375 mediated acquired chemo-resistance in cervical cancer by facilitating EMT.
abstract: Acquired chemo-resistance is one of the key causal factors in cancer death. Emerging evidences suggest that miRNA and epithelial-mesenchymal transition play critical roles in the chemo-resistance in cancers. Here, we showed the association of paclitaxel-resistance with miR-375 over-expression and epithelial-mesenchymal transition inducement in cervical cancer. Using different cervical cancer cell models, we found that paclitaxel transiently induced up-regulation of miR-375 expression, proliferation inhibition, transition from epithelial to mesenchymal phenotype, and consequently impaired paclitaxel sensitivity. Forced over-expression of miR-375 may suppress Ecadherin expression by a directly targeting pathway, which led to paclitaxel resistance. Contrarily, re-expression of Ecadherin partly reversed epithelial-mesenchymal transition phenotype and miR-375 induced paclitaxel-resistance. Our findings suggest that paclitaxel-induced miR-375 over-expression facilitates epithelial-mesenchymal transition process via directly targeting Ecadherin, proliferation inhibition, and consequently results in chemo-resistance in cervical cancer cells. A reversion of miR-375 or Ecadherin expression may be a novel therapeutic approach for overcoming chemo-resistance in cervical cancer.
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Jiansong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Xie
authors.affiliation: Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
mesh_terms: D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D025461:Feedback, Physiological / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D017239:Paclitaxel / Q000494:pharmacology; D010641:Phenotype; D015854:Up-Regulation / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D015820:Cadherins; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel