title: miR-200bc/429 cluster modulates multidrug resistance of human cancer cell lines by targeting BCL2 and XIAP.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are short non-coding RNA molecules, which post-transcriptionally regulate genes expression and play crucial roles in diverse biological processes. Recent studies have shown that dysregulation of miRNAs might modulate the resistance of cancer cells to anti-cancer drugs, yet the modulation mechanism is not fully understood. We aimed to investigate the possible role of miRNAs in the development of multidrug resistance (MDR) in human gastric and lung cancer cell lines.
  
  
  METHODS
  miRNA Quantitative real-time PCR was used to detect the different miRNA expression levels between drug resistant and parental cancer cells. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to test the drug-resistant phenotype changes in cancer cells via over or downregulation of miRNAs. Dual-luciferase activity assay was used to verify the target genes of miRNAs. Western blot analysis and apoptosis assay were used to elucidate the mechanism of miRNAs on modulating drug resistance in cancer cells.
  
  
  RESULTS
  miR-200bc/429 cluster was downregulated, while BCL2 and XIAP were upregulated in both MDR SGC7901/VCR (vincristine) and A549/CDDP (cisplatin) cells, compared with the parental SGC7901 and A549 cells, respectively. Overexpression of miR-200bc/429 cluster sensitized SGC7901/VCR and A549/CDDP cells to anti-cancer drugs, respectively. Both BCL2 and XIAP 3'-UTR reporters constructed in MDR cells suggested that BCL2 and XIAP were the common target genes of the miR-200bc/429 cluster. Enforced miR-200bc/429 cluster expression reduced BCL2 and XIAP protein level and sensitized both MDR cells to VCR-induced and CDDP-induced apoptosis, respectively.
  
  
  CONCLUSIONS
  Our findings first suggest that miR-200bc/429 cluster could play a role in the development of MDR in both gastric and lung cancer cell lines, at least in part by modulation of apoptosis via targeting BCL2 and XIAP.
authors: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors: Wei
authors: W
authors: Zhu
authors: Huaguo
authors: H
authors: Xu
authors: DanXia
authors: D
authors: Zhu
authors: Hui
authors: H
authors: Zhi
authors: Tongshan
authors: T
authors: Wang
authors: Jian
authors: J
authors: Wang
authors: Binghua
authors: B
authors: Jiang
authors: Yongqian
authors: Y
authors: Shu
authors: Ping
authors: P
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D005810:Multigene Family; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human