Chu Heying, Chen Xudong, Wang Huaqi, Du Yuwen, Wang Yuanyuan, Zang Wenqiao, Li Ping, Li Juan, Chang Jingxia, Zhao Guoqiang, Zhang Guojun
Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450052, Henan, China.
Tumour Biol. 2014 Apr;35(4):3487-94. doi: 10.1007/s13277-013-1460-1. Epub 2013 Nov 29.
Our previous studies have showed that metastasis-associated protein 3 (MTA 3) is overexpressed in non-small cell lung cancer (NSCLC) tissue, and increased MTA3 mRNA levels is a risk factor of lymph node metastasis. Using bioinformatics analyses, we found that MTA3 was a potential target of miR-495. However, the pathophysiological role of miR-495 and its relevance to the growth and development of NSCLC have yet to be investigated. The purpose of this study was to elucidate the molecular mechanisms by which miR-495 acts as a tumor suppressor in NSCLC. qRT-PCR data showed significant downregulation of miR-495 in 56 NSCLC tissue samples and 5 lung cancer cell lines, compared with their adjacent normal tissue; furthermore, western blotting analysis revealed MTA3 protein was overexpressed in the tumor samples compared with the matched adjacent normal tissue. MiR-495 was shown to not only inhibit the proliferation of lung cancer cells (A549 and Calu-3) but also to inhibit cell migration in vitro. Using western blotting and luciferase assays, MTA3 was identified as a target of miR-495. These findings suggest the importance of miR-495 targeting of MTA3 in the regulation of lung cancer growth and migration.
我们之前的研究表明，转移相关蛋白3（MTA 3）在非小细胞肺癌（NSCLC）组织中过表达，且MTA3 mRNA水平升高是淋巴结转移的一个危险因素。通过生物信息学分析，我们发现MTA3是miR - 495的一个潜在靶点。然而，miR - 495的病理生理作用及其与NSCLC生长发育的相关性尚未得到研究。本研究的目的是阐明miR - 495在NSCLC中作为肿瘤抑制因子发挥作用的分子机制。qRT - PCR数据显示，与相邻正常组织相比，56例NSCLC组织样本和5种肺癌细胞系中miR - 495显著下调；此外，蛋白质印迹分析显示，与匹配的相邻正常组织相比，肿瘤样本中MTA3蛋白过表达。结果表明，miR - 495不仅能抑制肺癌细胞（A549和Calu - 3）的增殖，还能在体外抑制细胞迁移。通过蛋白质印迹和荧光素酶测定，确定MTA3是miR - 495的一个靶点。这些发现表明miR - 495靶向MTA3在调节肺癌生长和迁移中具有重要作用。
