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The silencing of Bcl‑xL in the non‑small cell lung cancer (NSCLC) cell line, A549, downregulates miR‑361‑5p expression. This study aimed to determine the biological effects of miR‑361‑5p on NSCLC, and to elucidate the molecular mechanisms through which apoptosis is regulated. MicroRNA (miRNA or miR) functional analyses were performed via transfection of miR‑361‑5p mimics and inhibitors, demonstrating that the inhibition of miR‑361‑5p induced the apoptosis of NSCLC cells. To elucidate the function of miR‑361‑5p in vivo, cells transfected with miR‑361‑5p inhibitors were microinjected into zebrafish embryos, and immunostained using antibodies to detect the active form of caspase‑3. Co-transfection with siBcl‑xL and miR‑361‑5p mimics illustrated the association between Bcl‑xL, miR‑361‑5p and apoptosis; miR‑361‑5p mimics blocked the apoptosis initiated by siBcl‑xL. Luciferase reporter assays identified mothers against decapentaplegic homolog 2 (SMAD2) as a novel target of miR‑361‑5p and the reduction of its protein level was validated by western blot analysis. To confirm the molecular mechanisms through which apoptosis is regulated, gene rescue experiments revealed that the ectopic expression of SMAD2 attenuated the inhibitory effects on apoptosis induced by miR‑361‑5p. In this study, to the best of our knowledge, we provide the first evidence that miR‑361‑5p functions as an oncomiR in A549 and SK‑LU‑1 cells through the regulation of SMAD2, suggesting that miR‑361‑5p may be employed as a potential therapeutic target for the miRNA-based therapy of NSCLC.

Lung cancer remains a major health problem with a low 5-year survival rate of patients. Recent studies have shown that dysregulation of microRNAs (miRNAs) are prevalent in lung cancer and these aberrations play a significant role in the progression of tumour progression. In the present study, bioinformatics analyses was employed to predict potential miR-608 targets, which are associated with signaling pathways involved in cancer. Luciferase reporter assay identified AKT2 as a novel target of miR-608, and suppression of its protein levels was validated through western blot analysis. Zebrafish embryos were microinjected with cells transfected with miR-608 to elucidate the role of miR-608 in vivo, and immunostained with antibodies to detect activated caspase-3. We present the first evidence that miR-608 behaves as a tumour suppressor in A549 and SK-LU-1 cells through the regulation of AKT2, suggesting that selective targeting of AKT2 via miR-608 may be developed as a potential therapeutic strategy for miRNA-based non-small cell lung cancer (NSCLC) therapy.