MicroRNA-338-3p (miR-338-3p) has recently been reported to have anti-cancer efficacy in several types of cancers. However, its biological function and underlying mechanism involved in modulation of human non-small cell lung cancer (NSCLC) remain largely unknown. The present study was designed to investigate the function and underlying mechanism of miR-338-3p in human NSCLC tissues and cell lines. We demonstrated that miR-338-3p was significantly decreased in NSCLC tissues and cell lines, and negatively correlated with advanced and tumor-node-metastasis (TNM) stage and lymph node metastasis (both P<0.01). Transient overexpression of miR-338-3p by transfecting with miR-338-3p mimic significantly suppressed NSCLC cell proliferation, migration, invasion and induced apoptosis and cell cycle at G1 phase. Additionally, insulin receptor substrate 2 (IRS2), a known oncogene, was identified as a potential target gene of miR-338-3p. Subsequent investigations found a negative correlation between the expression of miR-338-3p and IRS2 in NSCLC tissues. Furthermore, overexpression of IRS2 reversed the effects of miR-338-3p in NSCLC cells on cell proliferation, cycle, apoptosis, migration, invasion. These findings suggested that miR-338-3p might act as a tumor suppressor by directly targeting IRS2 in NSCLC.
Keywords: IRS2; Non-small cell lung cancer; invasion; miR-338-3p; migration; proliferation.