MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma
MicroRNA-141 confers resistance to cisplatin-induced apoptosis by targeting YAP1 in human esophageal squamous cell carcinoma
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DOI：
10.1038/jhg.2011.1
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发表时间：
2011-04-01
影响因子：
3.5
通讯作者：
Tsujimoto, Gozoh
中科院分区：
文献类型：
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作者：
Imanaka, Yukako;Tsuchiya, Soken;Tsujimoto, Gozoh
MicroRNA (miRNA) 是内源性非编码 RNA，充当基因表达的负调节因子。 miRNA 表达的改变已被证明会影响肿瘤生长和对化疗的反应。在这项研究中，我们探讨了 miRNA 在食管鳞状细胞癌 (ESCC) 顺铂耐药中的可能作用。首先，我们使用体外细胞活力测定评估了九种人 ESCC 细胞系（KYSE 系列）对顺铂的敏感性，然后我们通过 miRNA 微阵列分析比较了顺铂敏感和耐药细胞系的 miRNA 谱。两组的 miRNA 表达谱存在显着差异，并且发现 10 个 miRNA 在两组之间受到差异性调控。当顺铂耐药细胞系中表达最高的 miRNA miR-141 在顺铂敏感细胞系中异位表达时，顺铂处理后细胞活力显着增加。此外，我们发现miR-141直接靶向YAP1的3'非翻译区，已知该区域在DNA损伤剂诱导的细胞凋亡中具有至关重要的作用，从而下调YAP1的表达。我们的研究强调了 miR-141 在 ESCC 顺铂耐药性发展中的重要调节作用。人类遗传学杂志 (2011) 56, 270-276; doi：10.1038/jhg.2011.1； 2011 年 2 月 3 日在线发布
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. Journal of Human Genetics (2011) 56, 270-276; doi:10.1038/jhg.2011.1; published online 3 February 2011