Background: EphA5 is a member of the Eph/ephrin family and plays a critical role in the regulation of carcinogenesis.\nA significant reduction of EphA5 transcripts in high-grade prostate cancer tissue was shown using a transcriptomic\nanalysis, compared to the low-grade prostate cancer tissue. As less is known about the mechanism of EphA5\ndownregulation and the function of EphA5, here we investigated the expression and an epigenetic change of EphA5\nin prostate cancer and determined if these findings were correlated with clinicopathologic characteristics of prostate\ncancer.\nMethods: Seven prostate cell lines (RWPE-1, LNCap, LNCap-LN3, CWR22rv-1, PC-3, PC-3M-LN4, and DU145), thirty-nine\nBPH, twenty-two primary prostate carcinomas, twenty-three paired noncancerous and cancerous prostate tissues were\nexamined via qRT-PCR, methylation-specific PCR, bisulfite sequencing, immunohistochemistry and western blotting. The\nrole of EphA5 in prostate cancer cell migration and invasion was examined by wound healing and transwell assay.\nResults: Downregulation or loss of EphA5 mRNA or protein expression was detected in 28 of 45 (62.2%) prostate\ncarcinomas, 2 of 39 (5.1%) hyperplasias, and all 6 prostate cancer cell lines. Methylation of the EphA5 promoter region\nwas present in 32 of 45 (71.1%) carcinoma samples, 3 of 39 (7.7%) hyperplasias, and the 6 prostate cancer cell lines.\nAmong 23 paired prostate carcinoma tissues, 16 tumor samples exhibited the hypermethylation of EphA5, and 15 of\nthese 16 specimens (93.8%) shown the downregulation of EphA5 expression than that of their respectively matched\nnoncancerous samples. Immunostaining analysis demonstrated that the EphA5 protein was absent or down-regulated\nin 10 of 13 (76.9%) available carcinoma samples, and 8 of these 10 samples (80.0%) exhibited hypermethylation. The\nfrequency of EphA5 methylation was higher in cancer patients with an elevated Gleason score or T3-T4 staging.\nFollowing the treatment of 6 prostate cancer cell lines with 5-aza-2?-deoxycytidine, the levels of EphA5 mRNA were\nsignificantly increased. Prostate cancer cells invasion and migration were significantly suppressed by ectopic expression\nof EphA5 in vitro.\nConclusion: Our study provides evidence that EphA5 is a potential target for epigenetic silencing in primary prostate\ncancer and is a potentially valuable prognosis predictor and thereapeutic marker for prostate cancer.
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