MicroRNA-320a is downregulated in non-small cell lung cancer and suppresses tumor cell growth and invasion by directly targeting insulin-like growth factor 1 receptor

摘要

Accumulating evidence has demonstrated that microRNAs (miRs/miRNAs) are implicated in carcinogenesis and cancer progression, and can function as oncogenes or tumor suppressor genes in human cancer types. Previous profile studies of miRNA expression levels have revealed that miR-320a was downregulated in breast cancer, colon cancer, bladder cancer, glioblastoma and salivary adenoid cystic carcinoma. However, its expression level, potential functions and the mechanisms underlying its functions in non-small cell lung cancer (NSCLC) require further investigation. The present study investigated the expression level, biological roles and underlying molecular mechanisms of miR-320a in NSCLC. The expression levels of miR-320a in NSCLC tissue and cell lines were detected using the reverse transcription-quantitative polymerase chain reaction. Cell proliferation and Transwell invasion assays were performed to examine the effects of miR-320a on NSCLC cells. In addition, bioinformatic analysis, western blot analysis and luciferase reporter assays were performed to identify the direct gene target of miR-320a in NSCLC. In the present study it was demonstrated that miR-320a was significantly downregulated in NSCLC tissues and cell lines. Ectopic overexpression of miR-320a suppressed the proliferation and invasion of NSCLC cells. Further studies indicated that miR-320a directly targeted the 3'-untranslated region of insulin-like growth factor 1 receptor (IGF-1R) and suppressed its expression at the mRNA and protein levels. As well as restoring the miR-320a expression level, the knockdown of IGF-1R also decreased the growth and invasion of the NSCLC cells. These results suggested that miR-320a served as a tumor suppressor in the NSCLC cells by directly targeting IGF-1R. Therefore, miR-320a should he investigated as a therapeutic target for the treatment of NSCLC.