DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer
DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer
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DLEC1 是一种 3p 肿瘤抑制因子，可抑制 NF-kappa B 信号传导并在前列腺癌中被甲基化
DOI：
10.1007/s00109-015-1255-5
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发表时间：
2015-06-01
影响因子：
4.7
通讯作者：
Jin, Jie
中科院分区：
文献类型：
--
作者：
Zhang, Lian;Zhang, Qian;Jin, Jie
位于3 p22-p21.3的肺癌和食管癌基因1（DLEC 1）参与多种癌症的发生，但其在前列腺癌（PrCa）中的作用尚不清楚。本文研究了DLEC 1基因的表观遗传学改变及其在前列腺癌中的作用。我们发现DLEC 1在正常前列腺组织、正常前列腺上皮细胞系（RWPE-1）和良性前列腺增生细胞系（BPH-1）中高度表达，但在PrCa细胞系中经常受到启动子甲基化的下调。药物去甲基化可以恢复DLEC 1表达。DLEC 1在前列腺肿瘤组织中的表达明显低于癌旁组织。DLEC 1在76/110例原发性肿瘤中甲基化，但在良性前列腺增生组织中很少甲基化。DLEC 1甲基化与较高的PSA水平（p = 0.016）、较高的Gleason评分（p = 0.015）和更晚期的肿瘤分期（p = 0.003）相关。此外，DLEC 1甲基化在PrCa患者的11/30尿沉渣样本中检测到，但很少在BPH患者的。DLEC 1的异位表达可通过诱导细胞凋亡抑制PrCa细胞的殖民地。DLEC 1也抑制PrCa细胞迁移。此外，DLEC 1抑制PrCa和HEK 293细胞中的NF-κ B转录活性。总之，我们的数据表明，DLEC 1作为一种肿瘤抑制因子，但在前列腺癌中经常甲基化。DLEC 1甲基化与前列腺癌进展相关，这可能是PrCa诊断的非侵入性表观遗传生物标志物。
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.