title: A Feedback Loop Between miR-30a/c-5p and DNMT1 Mediates Cisplatin Resistance in Ovarian Cancer Cells.
abstract: Many microRNAs (miRs) are dysregulated in cancers, and aberrant miR expression patterns have been suggested to correlate with chemo-resistance of cancer cells. We aim to study the role of miR-30 family members in cisplatin-resistance of ovarian cancer cells.
  
  
  
  qRT-PCR was used to compare differential expression levels of miR-30 family members in ovarian cancer cell line A2780 and its cisplatin-resistant derivative CP70. Changes of cisplatin-sensitivity in miR-30a-5p- and miR-30c-5p-overexpressed-CP70 cells and miR-30a-5p- and miR-30c-5p-inhibited-A2780 cells were examined by CCK8 assay and apoptosis analysis using flow cytometry; targets of miR-30a/c-5p were analyzed by western blotting and luciferase reporter assay; methylation regulation of pre-miR-30a/c-5p was examined by methylation specific PCR.
  
  
  
  miR-30a-5p and miR-30c-5p, in contrast to other miR-30 family members, dramatically decreased in cisplatin-resistant CP70 cells due to overexpressed-DNMT1 induced aberrant methylation. miR-30a/c-5p in turn directly inhibited DNMT1 as well as Snail. Forced expression of miR-30a/c-5p or knocking down of DNMT1 and Snail promoted cisplatin susceptibility and partially reversed epithelial-mesenchymal transition (EMT) in CP70 cells, while inhibition of miR-30a/c-5p or ectopic expression of DNMT1 and Snail induced cisplatin resistance and partial EMT in cisplatin-sensitive A2780 cells.
  
  
  
  A feedback loop between miR-30a/c-5p and DNMT1 is a potent signature for cisplatin-resistance and EMT in ovarian cancer, promising a potential target for improved anti-cancer treatment.
authors.forename: Xi
authors.initials: X
authors.lastname: Han
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhen
authors.forename: Zhongxue
authors.initials: Z
authors.lastname: Ye
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Lu
authors.forename: Lijie
authors.initials: L
authors.lastname: Wang
authors.forename: Pan
authors.initials: P
authors.lastname: Li
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.forename: Xia
authors.initials: X
authors.lastname: Zheng
authors.forename: Huijin
authors.initials: H
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: Le
authors.initials: L
authors.lastname: Zhao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D008156:Luciferases; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; D002945:Cisplatin
keywords: Cisplatin resistance; Epithelial-mesenchymal transition; Methylation; Ovarian cancer; microRNA