MiRNA-200a-3p suppresses the proliferation, migration and invasion of non-small cell lung cancer through targeting IRS2
MiRNA-200a-3p suppresses the proliferation, migration and invasion of non-small cell lung cancer through targeting IRS2
复制标题
miRNA-200a-3p通过靶向IRS2抑制非小细胞肺癌的增殖、迁移和侵袭
DOI：
10.26355/eurrev_202001_20050
复制
发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Wang, X. -W.
中科院分区：
文献类型：
--
作者：
Tan, T.;Xu, X. -H.;Wang, X. -W.
目的：为探讨microRNA-200 a-3 p（miRNA-200 a-3 p）在非小细胞肺癌（NSCLC）发生、发展中的生物学作用及其机制，采用真实的时间-聚合酶链反应（qRT-PCR）检测NSCLC组织和细胞系中miRNA-200 a-3 p和IRS 2的表达水平。分析miRNA-200 a-3 p表达水平与NSCLC病理特征的相关性。通过Kaplan-Meier方法评估miRNA-200 a-3 p在NSCLC中的预后价值。通过双荧光素酶报告基因分析和斯皮尔曼相关性检验探讨miRNA-200 a-3 p与IRS 2之间的潜在相互作用。采用CCK-8和transwell法检测miRNA-200 a-3 p/IRS 2对NSCLC细胞增殖、迁移和侵袭能力的调节作用。Western blot检测miRNA-200 a-3 p对NSCLC细胞中上皮间质转化（EMT）相关基因蛋白表达的影响。miRNA-200 a-3 p的表达水平与肿瘤大小、TNM分期、淋巴结转移有关。miRNA-200 a-3 p的低水平预测NSCLC患者的预后较差。miRNA-200 a-3 p的过表达抑制了A549细胞的增殖、迁移和侵袭。在过表达miRNA-200 a-3 p的A549细胞中，E-cadherin蛋白水平上调，而N-cadherin和Vimentin蛋白水平下调。双荧光素酶报告基因测定验证了miRNA-200 a-3 p和IRS 2之间的结合。IRS 2的表达水平受miRNA-200 a-3 p的负调控。结论：miRNA-200 a-3 p通过靶向IRS 2抑制NSCLC的增殖、迁移和侵袭能力，从而减缓NSCLC的进展。
OBJECTIVE: To uncover the biological role of microRNA-200a-3p (miRNA-200a-3p) in the progression of non-small cell lung cancer (NSCLC) and the underlying mechanism.PATIENTS AND METHODS: The expression levels of miRNA-200a-3p and IRS2 in NSCLC tissues and cell lines were examined through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the miRNA-200a-3p level and pathological characteristics of NSCLC patients was analyzed. The prognostic value of miRNA-200a-3p in NSCLC was assessed through the Kaplan-Meier method. The potential interaction between miRNA-200a-3p and IRS2 was explored through Dual-Luciferase Reporter Gene Assay and Spearman correlation test. The regulatory effects of miRNA-200a-3p/IRS2 on the proliferative, migratory, and invasive abilities of NSCLC were evaluated by Cell Counting Kit-8 (CCK-8) and the transwell assay. The protein levels of the epithelial-mesenchymal transition (EMT)-related genes in NSCLC cells influenced by miRNA-200a-3p were detected by Western blot.RESULTS: MiRNA-200a-3p was downregulated in NSCLC tissues and cell lines. The expression level of miRNA-200a-3p was related to tumor size, TNM staging, and lymphatic metastasis of NSCLC. The low level of miRNA-200a-3p predicted worse prognosis in NSCLC patients. The overexpression of miRNA-200a-3p inhibited A549 cells from proliferating, migrating, and invading. The protein levels of E-cadherin were upregulated, while N-cadherin and Vimentin were downregulated in A549 cells overexpressing miRNA-200a-3p. The Dual-Luciferase Reporter Gene Assay verified the binding between miRNA-200a-3p and IRS2. The level of IRS2 was negatively regulated by miRNA-200a-3p. Moreover, the overexpression of IRS2 could reverse the regulatory role of miRNA-200a-3p in the cellular behaviors of A549 cells.CONCLUSIONS: MiRNA-200a-3p suppresses the proliferative, migratory, and invasive abilities of NSCLC by targeting IRS2, thus alleviating the progression of NSCLC.