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.

据报道UNC5A与人类癌症有关。然而，在非小细胞肺癌（NSCLC）中的功能和机制仍然未知。我们分析了两种NSCLC细胞系（A549和H157），一种正常人支气管上皮细胞系（BEAS-2B）和NSCLC组织。我们使用定量实时PCR（qRT-PCR），蛋白质印迹和免疫组化（IHC）染色来检测UNC5A的表达。使用甲基化特异性PCR（MSP）和亚硫酸氢盐测序PCR（BSP）分析了UNC5A启动子的甲基化状态。我们使用蛋白质印迹分析了PI3K / Akt途径的蛋白质水平。我们发现UNCL5的mRNA表达在NSCLC细胞和组织中显着下调。与正常对照细胞相比，UNCCLA细胞的启动子在NSCLC细胞中被甲基化。脱甲基剂可以使NSCLC细胞中的UNC5A表达逆转。UNC5A的表达在NSCLC样品中降低，并且与晚期NSCLC类型显着相关。在功能上，敲除UNC5A可以促进NSCLC细胞增殖，迁移，侵袭并诱导细胞凋亡，UNC5A的过表达产生相反的结果。此外，我们发现UNC5A在NSCLC中负调控PI3K / Akt信号通路。UNC5A是NSCLC中一个新的表观遗传沉默基因，因此UNC5A的低表达可能通过调节PI3K / Akt途径促进NSCLC的肿瘤发生。侵袭和诱导NSCLC凋亡，UNC5A的过表达产生相反的结果。此外，我们发现UNC5A在NSCLC中负调控PI3K / Akt信号通路。UNC5A是NSCLC中一个新的表观遗传沉默基因，因此UNC5A的低表达可能通过调节PI3K / Akt途径促进NSCLC的肿瘤发生。侵袭和诱导NSCLC凋亡，UNC5A的过表达产生相反的结果。此外，我们发现UNC5A在NSCLC中负调控PI3K / Akt信号通路。UNC5A是NSCLC中一个新的表观遗传沉默基因，因此UNC5A的低表达可能通过调节PI3K / Akt途径促进NSCLC的肿瘤发生。