Non-small cell lung cancer (NSCLC) is one of the leading cause of death worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a promising anti-tumor agent with the ability to kill tumor cells while spare normal ones. MicroRNAs (miRNAs) are small, non-coding RNAs that play vital roles in carcinogenesis. Although miR-760 has been reported to be dysregulated in a variety of cancers, the role of miR-760 in NSCLC is not fully understood, and the relationship between miR-760 dysregulation and TRAIL sensitivity is still elusive. In the current study, we found that miR-760 is significantly downregulated in NSCLC tissues and cell lines. We also found that ectopic expression of miR-760, by targeting the FOXA1, enhanced TRAIL sensitivity in NSCLC cells. Correspondingly, silencing of FOXA1 also sensitized NSCLC cell to TRAIL-induced apoptosis and proliferation inhibition. In summary, these findings suggest that miR-760 should be considered as a tumor suppressor since it negatively regulates the oncogene protein FOXA1 and regulated TRAIL sensitivity in NSCLC cells.
Keywords: Apoptosis; FOXA1; NSCLC; TRAIL; miR-760.
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