UNC5A, an epigenetically silenced gene, functions as a tumor suppressor in non-small cell lung cancer

UNC5A has been reported to be related with human cancers. However, the function and mechanism in non-small cell lung carcinoma (NSCLC) remains unknown. We analyzed two NSCLC cell lines (A549 and H157), one normal human bronchial epithelial cell line (BEAS-2B) and the tissues of NSCLC. We used quantitative real-time PCR (qRT-PCR), western blot and immunohistochemical (IHC) staining to examine the expression of UNC5A. Methylation status of the UNC5A promoter was analyzed using methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP). We used western blot to analyzed protein levels of PI3K/Akt pathway. We found that the mRNA expression of UNCA5 was significantly downregulated in NSCLC cells and tissues. The promoter of UNC5A was hypermethylated in NSCLC cells compared to normal control cells. The expression of UNC5A could be reversed by demethylation agent in NSCLC cells. The expression of UNC5A was decreased in NSCLC samples and significantly associated with the advanced types of NSCLC. Functionally, knockdown of UNC5A promoted cell proliferation, migration, invasion and induced apoptosis in NSCLC, overexpression of UNC5A yielded the opposite result. Moreover, we found that UNC5A negatively regulated PI3K/Akt signaling pathway in NSCLC. UNC5A is a novel epigenetically silenced gene in NSCLC and consequent under-expression of UNC5A may contribute to NSCLC tumorigenesis through regulating PI3K/Akt pathway.