MiR-454 promotes the progression of human non-small cell lung cancer and directly targets PTEN.

PURPOSE

MicroRNA-454 has been proven dysregulated in some human malignancies and correlated with tumor progression. However, its expression and function in non-small cell lung cancer (NSCLC) is still unclear. Thus, the aim of this study was to explore the effects of miR-454 in NSCLC tumorigenesis and development.

METHODS

Using quantitative RT-PCR, we detected miR-454 expression in NSCLC cell lines and primary tumor tissues. The association of miR-454 expression with clinicopathological factors and prognosis was also analyzed. Then, the effects of miR-454 on the biological behavior of NSCLC cells were investigated. At last, the potential regulatory function of miR-454 on PTEN expression was confirmed.

RESULTS

miR-454 was found to be up-regulated in NSCLC tissues and cell lines. High miR-454 expression was closely correlated with lymph node metastasis, advanced TNM stage, and shorter overall survival. Multivariate regression analysis corroborated that miR-454 overexpression was an independent unfavourable prognostic factor for patients with NSCLC. Down-regulation of miR-454 could significantly reduce NSCLC cell proliferation, enhance cell apoptosis, and impair cell invasion and migration in vitro, while up-regulation of miR-454 showed opposite effects. Further, PTEN was confirmed as a direct target of miR-454 by using Luciferase Reporter Assay.

CONCLUSIONS

These findings indicate that miR-454 may act as an oncogene in NSCLC and would serve as a potential therapy target for this disease.