title: MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma.
abstract: MicroRNAs (miRNAs) are endogenous non-coding RNAs that function as negative regulators of gene expression. Alterations in miRNA expression have been shown to affect tumor growth and response to chemotherapy. In this study, we explored the possible role of miRNAs in cisplatin resistance in esophageal squamous cell carcinoma (ESCC). First we assessed the sensitivity of nine human ESCC cell lines (KYSE series) to cisplatin using an in vitro cell viability assay, and then we compared the miRNA profiles of the cisplatin-sensitive and -resistant cell lines by miRNA microarray analysis. The two groups showed markedly different miRNA expression profiles, and 10 miRNAs were found to be regulated differentially between the two groups. When miR-141, which was the most highly expressed miRNA in the cisplatin-resistant cell lines, was expressed ectopically in the cisplatin-sensitive cell lines, cell viability after cisplatin treatment was increased significantly. Furthermore, we found that miR-141 directly targeted the 3'-untranslated region of YAP1, which is known to have a crucial role in apoptosis induced by DNA-damaging agents, and thus downregulated YAP1 expression. Our study highlights an important regulatory role for miR-141 in the development of cisplatin resistance in ESCC.
authors.affiliation: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Imanaka
authors.forename: Soken
authors.initials: S
authors.lastname: Tsuchiya
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Shimizu
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002945:Cisplatin / Q000378:metabolism / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D010750:Phosphoproteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D014343:Trypan Blue; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C533895:MIRN141 microRNA, human; D035683:MicroRNAs; D010750:Phosphoproteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D014343:Trypan Blue; D002945:Cisplatin