MicroRNA-15b promotes proliferation and invasion of non-small cell lung carcinoma cells by directly targeting TIMP2

Abstract

MicroRNA-15b (miR-15b) plays an important role in tumor development and progression. miR-15b functions differently in various types of malignant tumors. However, the expression pattern and role of miR-15b in non-small cell lung cancer (NSCLC) have not been elucidated. In the present study, we investigated the effect of miR-15b on the occurrence and development of lung cancer and the underlying mechanism. Lung cancer cell lines A549 and LTEP-a-2 were transfected with miR-15b inhibitor or mimic, respectively. Real-time PCR revealed that the expression level of miR-15b was significantly higher in human NSCLC tissues and NSCLC cells, than that of normal tissues and cells, respectively (P<0.05). Moreover, the effect of miR-15b on A549 and LTEP-a-2 cell viability, cell cycle, migration and invasion was further evaluated. Experiments indicated that miR-15b knockdown inhibited the viability, cell cycle, migration and invasion in A549 cells, while upregulation of miR-15b exhibited the opposite effect. Tissue inhibitor of metallopeptidases 2 (TIMP2) protein and mRNA levels were downregulated after miR-15b overexpression in A549 and LTEP-a-2 cells, respectively. The dual-luciferase reporter gene assay implied that TIMP2 is a direct target gene of miR-15b. Our results indicate that high expression of miR-15b is associated with NSCLC and suggest that miR-15b expression may be a novel biomarker for predicting clinical outcomes in NSCLC patients. The inhibition of miR-15b may even provide helpful therapeutic strategies for the treatment of NSCLC.