MicroRNA-661 promotes non-small cell lung cancer progression by directly targeting RUNX3

Abstract

Lung cancer is the primary cause of cancer-associated mortality in men and women worldwide. Increasing evidence indicates that abnormal microRNA (miRNA) expression contributes to the carcinogenesis and progression of multiple human cancers, including non-small cell lung cancer (NSCLC). Therefore, miRNAs exhibit the potential to act as biomarkers for the diagnosis, treatment and prognosis of human malignancies. miRNA-661 (miR-661) has previously been demonstrated to be important in the development of various human cancer types. However, the expression levels, functions and underlying mechanisms of miR-661 in NSCLC remain to be elucidated. The present study demonstrated that miR-661 was upregulated in NSCLC tissues and cell lines. In addition, miR-661 expression levels were significantly correlated with differentiation and tumor stage lymph node metastasis of NSCLC patients. Functional experiments demonstrated that miR-661 downregulation inhibited NSCLC cell proliferation and invasion in vitro. Furthermore, runt-related transcription factor 3 (RUNX3) was identified as a direct target of miR-661 in NSCLC. RUNX3 was expressed at a low level in NSCLC tissues and was negatively correlated with the miR-661 expression level. Further experiments revealed that RUNX3 knockdown significantly rescued the effects of miR-661 underexpression on NSCLC cell proliferation and invasion. In conclusion, the present findings indicated a role for miR-661 as an oncogene in NSCLC via direct targeting of RUNX3, thus suggesting that miR-661 may be used to develop novel therapies for NSCLC patients.