MiRNA-200a-3p suppresses the proliferation, migration and invasion of non-small cell lung cancer through targeting IRS2

T. Tan, X.-H. Xu, X.-H. Lu, X.-W. Wang

Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. wangxiaowei@njmu.edu.cn

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• Oncology

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.

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