title: MiR-18a upregulation enhances autophagy in triple negative cancer cells via inhibiting mTOR signaling pathway.
abstract: We investigated the involvement of miR-18a upregulation in autophagy regulation and paclitaxel (PTX) resistance in triple negative breast cancer (TNBC) cells.
  
  
  
  PTX resistant MDA-MMB-231/PTX cells were generated using an intermittent, stepwise method. MiR-18a expression was assessed using qRT-PCR. The level of autophagy was assessed by Western blot analysis of LC3B expression and observation of LC3-GFP puncta formation under a fluorescence microscope. The effect of miR-18a mediated autophagy on PTX sensitivity was assessed by measuring IC50 and PTX induced cell apoptosis.
  
  
  
  MDA-MB-231/PTX cells had both higher miR-18a expression and basal autophagy than MDA-MB-231 cells. Enforced miR-18a overexpression directly led to increased autophagy in MDA-MB-231 cells, the effect of which was similar to that of rapamycin, a mTOR signaling inhibitor. Following Western blot analysis showed that miR-18a overexpression decreased the expression of p-mTOR and p-p70S6. Therefore, we infer that miR-18a increases autophagy level in MDA-MB-231 cells via inhibiting mTOR signaling pathway. Both drug sensitivity assay and flow cytometry analysis confirmed that the effect of miR-18a on increasing IC50 and decreasing PTX induced apoptosis in MDA-MB-231 cells could largely be abrogated by treatment with bafilomycin A1 (Baf. A1).
  
  
  
  MiR-18a upregulation results in enhanced autophagy via inhibiting mTOR signaling pathway in TNBC cells, which is a mechanism contributing to paclitaxel resistance.
authors.affiliation: Clinical Laboratory, the People's Hospital of Gaomi, Gaomi, Shandong, China. huizhange@outlook.com.
authors.forename: Y-X
authors.initials: YX
authors.lastname: Fan
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Dai
authors.forename: X-L
authors.initials: XL
authors.lastname: Wang
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Ren
authors.forename: J-J
authors.initials: JJ
authors.lastname: Han
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C522576:MIRN18A microRNA, human; D035683:MicroRNAs; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases