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miR-543在吉非替尼耐药的非小细胞肺癌中上调,并通过磷酸酶和张力蛋白同源物促进细胞增殖和侵袭。

miR-543 is up-regulated in gefitinib-resistant non-small cell lung cancer and promotes cell proliferation and invasion via phosphatase and tensin homolog.

作者信息

Bi Mingjun, Chen Wei, Yu Hongmei, Wang Jinxiu, Ding Fang, Tang Dong Jing, Tang Cuiyan

机构信息

Department of General Surgery, Weihai Woman and Children's Hospital, 51 Guangming Road, Weihai 264200, PR China.

Department of Breast Surgery, Weihai Woman and Children's Hospital, 51 Guangming Road, Weihai 264200, PR China.

出版信息

Biochem Biophys Res Commun. 2016 Nov 18;480(3):369-374. doi: 10.1016/j.bbrc.2016.10.055. Epub 2016 Oct 18.

DOI:10.1016/j.bbrc.2016.10.055
PMID:27769862
Abstract

MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we identified that miR-543 is up-regulated in gefitinib-resistant non-small cell lung cancer (NSCLC) patients comparing gefitinib-sensitive ones. It promotes NSCLC cell proliferation by negatively regulates its target gene PTEN. In NSCLC cell lines, CCK-8 proliferation assay indicated that the cell proliferation is promoted by miR-543 mimics. Transwell assay showed that miR-543 mimics promotes the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-543 directly binds to the 3'untranslated region of PTEN, and western blotting showed that miR-543 suppresses the expression of PTEN at the protein level. This study indicates that miR-543 promotes proliferation and invasion of NSCLC cell lines by PTEN. The miR-543 may represent a potential therapeutic target for gefitinib-resistant NSCLC intervention.

摘要

微小RNA(miRNA)通过在转录后水平负调控基因表达,在多种癌症的发病机制中发挥重要作用。在此,我们发现与吉非替尼敏感的非小细胞肺癌(NSCLC)患者相比,miR-543在吉非替尼耐药的NSCLC患者中表达上调。它通过负调控其靶基因PTEN来促进NSCLC细胞增殖。在NSCLC细胞系中,CCK-8增殖试验表明miR-543模拟物可促进细胞增殖。Transwell试验表明miR-543模拟物可促进NSCLC细胞的侵袭和迁移。荧光素酶试验证实miR-543直接与PTEN的3'非翻译区结合,蛋白质印迹法表明miR-543在蛋白质水平上抑制PTEN的表达。本研究表明,miR-543通过PTEN促进NSCLC细胞系的增殖和侵袭。miR-543可能是吉非替尼耐药NSCLC干预的潜在治疗靶点。

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