MicroRNA-208a directly targets Src kinase signaling inhibitor 1 to facilitate cell proliferation and invasion in non-small cell lung cancer

The abnormal expression of microRNAs (miRNAs/miRs) has a critical function in the formation and progression of non-small cell lung cancer (NSCLC). Therefore, understanding the association between NSCLC and dysregulated miRNAs may allow for the identification of novel diagnostic and therapeutic biomarkers for patients with this malignancy. Previous studies have validated miR-208a as a cancer-associated miRNA in multiple different types of human cancer, however, its expression pattern and precise function in NSCLC remains yet to be elucidated. Therefore, the aims of the present study were to measure miR-208a expression in NSCLC, investigate its specific functions in NSCLC and determine its exact regulatory mechanisms. Herein, the results demonstrated that miR-208a was significantly upregulated in NSCLC tissues and cell lines compared with that in adjacent non-cancerous tissues and a non-tumorigenic bronchial epithelium BEAS-2B cell line (P<0.05, respectively). The high expression level of miR-208a exhibited an obvious association with Tumor-Node-Metastasis stage and lymph node metastasis. miR-208a silencing decreased the proliferative and invasive capacities of NSCLC cells. Notably, Src kinase signaling inhibitor 1 (SRCIN1) was verified as a potential direct target gene of miR-208a in NSCLC cells. Furthermore, SRCIN1 knockdown was able to rescue the miR-208a-mediated effects on NSCLC cells. In addition to this, silencing miR-208a expression inhibited the extracellular regulated kinase (ERK) signaling pathway in NSCLC. Overall, to the best of our knowledge, the present study is the first to provide evidence that miR-208a exerts oncogenic functions in the carcinogenesis and progression of NSCLC by directly targeting SRCIN1 and regulating the ERK pathway. Therefore, miR-208a may be developed as a potential target for treating patients with NSCLC.