MiR-484 promotes non-small-cell lung cancer (NSCLC) progression through inhibiting Apaf-1 associated with the suppression of apoptosis.

Increasing studies have indicated that the dysregulated microRNAs (miRNAs) are associated with tumorigenesis, development and even the poor prognosis of a variety of tumors, including the non-small-cell lung cancer (NSCLC). Here in our study, we found that miRNA-484 was expressed highly in NSCLC clinical tumor samples in comparison to the matched adjacent tissues. In addition, high and low expression of miRNA-484 was observed in NSCLC cell lines and lung normal cells, respectively. Furthermore, the capability of migration and proliferation changed accompanied with the altered expression of miR-484 in NSCLC. Apoptotic protease activating factor-1 (APAF-1), frequently down-regulated in a number of types of cancer, was found to be reduced in NSCLC tissue samples or NSCLC cell lines along with high expression of miR-484, which were inversely expressed in Apaf-1 over-expressed tissues or cells. Moreover, miR-484 triggered the migration and proliferation, and simultaneously reduced the cleavage of poly (ADP-ribose) polymerase-2 (PARP-2) and Caspase-3 of A549 cells, which could be suppressed by the improvement of Apaf-1. And the inhibition of Apaf-1 could reverse the function caused by miR-484 in A549 cells, suggesting that Apaf-1 was targeted by miR-484 directly and it could be acted as a potential therapeutic target against NSCLC. In conclusion, the reductive Apaf-1 regulated by miR-484 accelerated the NSCLC cell progression associated with the inhibition of apoptosis via down-regulating Caspase-3 and PARP cleavage.