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miR-205 通过靶向 PTEN 促进 NSCLC 细胞的生长、转移和化疗耐药性。

miR-205 promotes the growth, metastasis and chemoresistance of NSCLC cells by targeting PTEN.

机构信息

Department of Oncology, Xiangyang Central Hospital, Xiangyang 441021, P.R. China.

出版信息

Oncol Rep. 2013 Dec;30(6):2897-902. doi: 10.3892/or.2013.2755. Epub 2013 Sep 30.

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common causes of cancer-related mortality worldwide. microRNAs (miRNAs) play critical roles in carcinogenesis. miR-205 has been shown to be upregulated in NSCLC. In the present study, we identified the promotive effects of miR-205 on various significant biological properties of NSCLC cells, and confirmed the regulation of PTEN by miR-205. The expression of miR-205 was examined by quantitative real-time PCR both in NSCLC cell lines and tissues. The effect of miR-205 on PTEN expression was assessed in NSCLC cell lines with miR-205 mimics/inhibitor to elevate/decrease miR-205 expression. Furthermore, the roles of miR-205 in regulating the biological properties of NSCLC cells, including growth, invasion and chemoresistance, were assayed using miR-205 mimic/inhibitor-transfected cells. The 3'-untranslated region (3'-UTR) of PTEN combined with miR-205 and this was confirmed by luciferase reporter assay and western blotting. miR-205 expression was increased in NSCLC cell lines as well as in tissues. Overexpression of miR-205 promoted growth, migration and invasion, and enhanced the chemoresistance of NSCLC cells. Luciferase activity and western blotting demonstrated that miR-205 negatively regulated PTEN at a posttranscriptional level. However, miR-205 knockdown suppressed these processes in A549 cells and increased the expression of PTEN protein. Furthermore, overexpression of PTEN exhibited effects identical with those of the miR-205 inhibitor in NSCLC cells. Our results demonstrated that miR-205 is involved in the tumorigenesis of NSCLC through modulation of the PTEN signaling pathway.

摘要

非小细胞肺癌(NSCLC)是全球癌症相关死亡的最常见原因之一。microRNAs(miRNAs)在癌症发生中起关键作用。miR-205 在 NSCLC 中被证明上调。在本研究中,我们确定了 miR-205 对 NSCLC 细胞各种重要生物学特性的促进作用,并证实了 miR-205 对 PTEN 的调节作用。通过定量实时 PCR 检测 NSCLC 细胞系和组织中 miR-205 的表达。通过 miR-205 模拟物/抑制剂在 NSCLC 细胞系中上调/下调 miR-205 表达,评估 miR-205 对 PTEN 表达的影响。此外,通过 miR-205 模拟物/抑制剂转染细胞,检测 miR-205 在调节 NSCLC 细胞生物学特性(包括生长、侵袭和化疗耐药性)中的作用。PTEN 的 3'-非翻译区(3'-UTR)与 miR-205 结合,并通过荧光素酶报告基因检测和 Western blot 证实。miR-205 在 NSCLC 细胞系和组织中表达增加。miR-205 的过表达促进了 NSCLC 细胞的生长、迁移和侵袭,并增强了其化疗耐药性。荧光素酶活性和 Western blot 表明,miR-205 在转录后水平负调控 PTEN。然而,miR-205 敲低抑制了 A549 细胞中的这些过程,并增加了 PTEN 蛋白的表达。此外,PTEN 的过表达在 NSCLC 细胞中表现出与 miR-205 抑制剂相同的作用。我们的研究结果表明,miR-205 通过调节 PTEN 信号通路参与 NSCLC 的肿瘤发生。

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