miR-223 inhibits tumor development of non-small cell lung cancer and sensitizes cancer cells to gefitinib via targeting E 2 F 1

MicroRNAs (miRNAs) are a class of short and non-coding RNA molecules that are capable of inhibiting translation of mRNAs of target genes. Previous studies have revealed that miRNAs are involved in the tumorigenesis and development of lung cancer. The Rnase-resistance of circulating miRNAs made it valuable non-invasive biomarkers and had attracted extensive research interests. The aim of the present study was to investigate the role of miR-223 in non-small cell lung cancer (NSCLC). The miRNA profiling showed a significantly differential expression of miR-205 and miR-223 between NSCLC tissue and normal adjacent tissues. Higher serum miR-233 level is corresponding to better survival, while miR-205 did not show difference regarding correlation of survival rate with its expression level. Using TargetScan predicting server, E2F1 was selected as a candidate target of miR-223, which was validated via luciferase assay. Further, overexpression of E2F1 counteracted the inhibitory effect of miR-223 on cell proliferation, and alleviates the proapoptosis by miR-223. Considering the deregulation of E2F1 had been reported in chemoresistant cells, we investigated the role of miR-223 in gefitinib challenged A549 cells. The tumor volume growth of mice injected with cells carrying lentivirus mediated miR-223 showed significantly decrease than control when both group treated with gefitinib on 15th day, which is consistent with survival analysis of those nude mice. These evidences point to the prospect of utilizing miR-223 in the prognosis of NSCLC patients under chemotherapy.