title: miR-375 is upregulated in acquired paclitaxel resistance in cervical cancer.
abstract: BACKGROUND
  Chemo-resistance is one of the key causal factors in cancer death and emerging evidences suggest that microRNAs (miRNAs) have critical roles in the regulation of chemo-sensitivity in cancers. Cervical cancer is one of the most common malignancies in women and insensitive to chemotherapy clinically.
  
  
  METHODS
  The differentially expressed miRNAs in cervical squamous cell carcinoma tissues were screened by using a microarray platform (μParaflo Sanger miRBase release 13.0). The expression of miR-375 was determined by stem-loop RT-PCR using 23 clinical cervical cancer samples and 2 cervical cancer cell lines. We exogenously upregulated miR-375 expression in SiHa and Caski cells using a pre-miRNA lentiviral vector transfection and observed its impact on paclitaxel sensitivity using MTS. The cells that stably overexpressed miR-375 were subcutaneously injected into mice to determine tumour growth and chemo-sensitivity in vivo.
  
  
  RESULTS
  Twenty-one differentially expressed miRNAs were found by miRNA microarray between pro- and post-paclitaxel cervical cancer tissues. Of those, miR-375 showed consistent high expression levels across paclitaxel-treated cervical cells and tissues. Paclitaxel induced upregulated miR-375 expression in a clear dose-dependent manner. Forced overexpression of miR-375 in cervical cancer cells decreased paclitaxel sensitivity in vitro and in vivo.
  
  
  CONCLUSIONS
  Collectively, our results suggest that miR-375 might be a therapeutic target in paclitaxel-resistant cervical cancer.
authors.affiliation: Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shen
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Ye
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Wan
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.forename: W
authors.initials: W
authors.lastname: Lu
authors.forename: X
authors.initials: X
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D017239:Paclitaxel / Q000627:therapeutic use*; D015854:Up-Regulation; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel