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学科主题: 临床医学
题名:
DLEC1, a 3p tumor suppressor, represses NF-kappa B signaling and is methylated in prostate cancer
作者: Zhang, Lian1,2; Zhang, Qian1,2; Li, LiLi3,4; Wang, Zhaohui3,4; Ying, Jianming5,6; Fan, Yu1,2; He, Qun1,2; Lv, Tianjing1,2; Han, Wenke1,2; Li, Jun1,2; Yang, Yang1,2; Xu, Ben1,2; Wang, Lu1,2; Liu, Qianling1,2; Sun, Yinghao7; Guo, Yinglu1,2; Tao, Qian3,4; Jin, Jie1,2
关键词: DLEC1 ; Prostate cancer ; Tumor suppressor gene ; Methylation ; NF-kappa B
刊名: JOURNAL OF MOLECULAR MEDICINE-JMM
发表日期: 2015-06-01
DOI: 10.1007/s00109-015-1255-5
卷: 93, 期:6, 页:691-701
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Genetics & Heredity ; Medicine, Research & Experimental
研究领域[WOS]: Genetics & Heredity ; Research & Experimental Medicine
关键词[WOS]: DNA METHYLATION ; GSTP1 HYPERMETHYLATION ; PROMOTER METHYLATION ; MOLECULAR-DETECTION ; GENE DLEC1 ; CARCINOMA ; URINE ; TUMORIGENESIS ; ACTIVATION ; DISEASE
英文摘要:

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.

语种: 英语
所属项目编号: 81272290 ; 81171971 ; 81372898 ; 81101492 ; Z131107002213130 ; Z121107002512012 ; W2013BJ28 ; GJHS20120702105523309 ; 2012CB518305
项目资助者: National Natural Science Foundation ; Beijing Municipal Science and Technology Commission ; Central Health Care Research Foundation ; Shenzhen city ; China 973 Program
WOS记录号: WOS:000354474400010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64079
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Natl Res Ctr Genitourinary Oncol, Dept Urol, Beijing 100871, Peoples R China
2.Inst Urol, Beijing, Peoples R China
3.Chinese Univ Hong Kong, Dept Clin Oncol, Sir YK Pao Ctr Canc, Canc Epigenet Lab,State Key Lab Oncol South China, Shatin, Hong Kong, Peoples R China
4.CUHK, Shenzhen Res Inst, Shatin, Hong Kong, Peoples R China
5.Chinese Acad Med Sci, Peking Union Med Coll, Inst Canc, Dept Pathol, Beijing 100730, Peoples R China
6.Chinese Acad Med Sci, Peking Union Med Coll, Canc Hosp, Beijing 100730, Peoples R China
7.Second Mil Med Univ, Dept Urol, Shanghai Changhai Hosp, Shanghai, Peoples R China

Recommended Citation:
Zhang, Lian,Zhang, Qian,Li, LiLi,et al. DLEC1, a 3p tumor suppressor, represses NF-kappa B signaling and is methylated in prostate cancer[J]. JOURNAL OF MOLECULAR MEDICINE-JMM,2015,93(6):691-701.
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