Endogenous microRNA-424 predicts clinical outcome and its inhibition acts as cancer suppressor in human non-small cell lung cancer.

PURPOSE: We examined the expression, clinical correlation and functional mechanisms of endogenous microRNA-424 (miR-424) in human non-small cell lung cancer (NSCLC).

METHODS: Expression pattern of endogenous miR-424 was examined by qRT-PCR in clinical samples obtained from 233 NSCLC patients. Correlations between differential miR-424 expression level (low vs. high) and NSCLC patients' clinicopathological parameters or survival were statistically examined. In in vitro NSCLC H596 and SW900 cells, miR-424 was either upregulated or downregulation by lentiviral transduction. Their effects on cancer cell viability, proliferation, and cell-cycle transition were also examined.

RESULTS: MiR-424 expression was not different between NSCLC tumors and healthy lung tissues. However, it is much upregulated in NSCLC tumors associated with patients at advanced clinical stages. Statistical analyses demonstrated that high endogenous miR-424 expression in NSCLC tumors was significantly correlated with patients' advanced clinical stages, aggressive tumor metastasis, and short survival. In addition, Cox regression model predicted that endogenous miR-424 might be an independent prognostic marker in NSCLC. In in vitro NSCLC cell lines, miR-424 downregulation had a significant suppressing effect on cancer proliferation and G1 to S phase cell-cycle transition. On the other hand, miR-424 upregulation had no effect on NSCLC in vitro.

CONCLUSION: High endogenous miR-424 expression in tumors may predict poor prognosis of patients with NSCLC. Inhibiting endogenous miR-424 may also serve an effective cancer suppressor in NSCLC.