DLEC1, a 3p tumor suppressor, represses NF-kappa B signaling and is methylated in prostate cancer
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摘要Deleted in lung and esophageal cancer 1 (DLEC1), located at 3p22-p21.3, is involved in the carcinogenesis of multiple cancers, but its role in prostate cancer (PrCa) remains unclear. Here, we studied the epigenetic alteration of DLEC1 and its functions in prostate cancer. We found that DLEC1 was highly expressed in normal prostate tissues, normal prostatic epithelium cell line (RWPE-1), and benign prostatic hyperplasia cell line (BPH-1), but frequently downregulated by promoter methylation in PrCa cell lines. Pharmacologic demethylation could restore DLEC1 expression. DLEC1 was downregulated in prostate tumor tissues compared with their adjacent non-malignant tissues. DLEC1 was methylated in 76/110 primary tumors, but rarely in benign prostatic hyperplasia tissues. DLEC1 methylation was associated with higher PSA levels (p = 0.016), higher Gleason scores (p = 0.015), and more advanced tumor stages (p = 0.003). Furthermore, DLEC1 methylation was detected in 11/30 urine sediment samples from PrCa patients, but seldom in ones from BPH patients. Ectopic expression of DLEC1 inhibited the colony formation of PrCa cells, through inducing cell apoptosis. DLEC1 also suppressed PrCa cell migration. Moreover, DLEC1 inhibited NF-kappa B transcription activity in PrCa and HEK293 cells. Taken together, our data demonstrate that DLEC1 functions as a tumor suppressor but is frequently methylated in prostate cancer. DLEC1 methylation is associated with prostate cancer progression, which could be a non-invasive epigenetic biomarker for PrCa diagnosis.
著者Zhang L, Zhang Q, Li LL, Wang ZH, Ying JM, Fan Y, He Q, Lv TJ, Han WK, Li J, Yang Y, Xu B, Wang L, Liu QL, Sun YH, Guo YL, Tao Q, Jin J
期刊名稱Journal of Molecular Medicine
出版年份2015
月份6
日期1
卷號93
期次6
出版社Springer Verlag (Germany)
頁次691 - 701
國際標準期刊號0946-2716
電子國際標準期刊號1432-1440
語言英式英語
關鍵詞DLEC1; Methylation; NF-kappa B; Prostate cancer; Tumor suppressor gene
Web of Science 學科類別Genetics & Heredity; Medicine, Research & Experimental; Research & Experimental Medicine

上次更新時間 2020-05-12 於 23:04