title: MiR-18a upregulation decreases Dicer expression and confers paclitaxel resistance in triple negative breast cancer.
abstract: MiR-18a is a miRNA that is aberrantly overexpressed in triple-negative breast cancer (TNBC). However, its biophysical function in TNBC is still not clear. In this study, we investigated the association among miR-18a dysregulation, Dicer dysregulation and paclitaxel (PTX) resistance in TNBC cells.
  
  
  
  20 TNBC patients who received neoadjuvant chemotherapy before surgery were recruited. MiR-18a expression was quantified using QRT-PCR. The effects of miR-18a overexpression or knockdown on cell viability and apoptosis of PTX sensitive MDA-MB-231 cells and PTX resistant MDA-MB-231 cells after PTX treatment were studied. The influence of miR-18a overexpression on Dicer expression was measured by qRT-PCR and Western blot analysis.
  
  
  
  Tissues from patients with stable disease (SD, n = 5) and progressive disease (PD, n = 2) to paclitaxel (PTX) containing neoadjuvant chemotherapy had significantly higher miR-18a expression than that from patients with partial response (PR, n = 13). MDA-MB-231/PTX cells had higher miR-18a expression than MDA-MB-231 cells. MiR-18a overexpression directly led to Dicer repression at mRNA and protein level. MiR-18a overexpression significantly increased PTX IC50 and reduced PTX induced cell apoptosis, while miR-18a suppression substantially decreased PTX IC50 and increased PTX induced cell apoptosis.
  
  
  
  This study found that miR-18a is an important miRNA that suppresses Dicer expression and increases PTX resistance in TNBC cells.
authors.affiliation: Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Huizhange@outlook.com.
authors.forename: L-Y
authors.initials: LY
authors.lastname: Sha
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Sui
authors.forename: S-K
authors.initials: SK
authors.lastname: Liu
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: C522576:MIRN18A microRNA, human; D035683:MicroRNAs; D017239:Paclitaxel