Open AccessmiR-375 Mediated Acquired Chemo-Resistance in Cervical Cancer by Facilitating EMT
Author(s) -
Yuanming Shen,
Jiansong Zhou,
Yang Li,
Feng Ye,
Xiaoxia Wan,
Weiguo Lü,
Xing Xie,
Xiaodong Cheng
Publication year - 2014
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0109299
Subject(s) - paclitaxel , epithelial–mesenchymal transition , cancer research , microrna , mesenchymal stem cell , cervical cancer , cancer , reversion , drug resistance , biology , phenotype , medicine , metastasis , microbiology and biotechnology , gene , genetics
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.