title: DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer.
abstract: 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-κB 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.
  
  
  CONCLUSIONS
  • Promoter methylation of DLEC1 is a potential prognostic biomarker for PrCa. • DLEC1, a functional tumor suppressor, is frequently methylated in PrCa. • DLEC1 suppresses prostate cancer growth and metastatic behavior. • DLEC1 mediates tumor-suppressive activities through NF-κB signaling.
authors: Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China.
authors: Lian
authors: L
authors: Zhang
authors: Qian
authors: Q
authors: Zhang
authors: LiLi
authors: L
authors: Li
authors: Zhaohui
authors: Z
authors: Wang
authors: Jianming
authors: J
authors: Ying
authors: Yu
authors: Y
authors: Fan
authors: Qun
authors: Q
authors: He
authors: Tianjing
authors: T
authors: Lv
authors: Wenke
authors: W
authors: Han
authors: Jun
authors: J
authors: Li
authors: Yang
authors: Y
authors: Yang
authors: Ben
authors: B
authors: Xu
authors: Lu
authors: L
authors: Wang
authors: Qianling
authors: Q
authors: Liu
authors: Yinghao
authors: Y
authors: Sun
authors: Yinglu
authors: Y
authors: Guo
authors: Qian
authors: Q
authors: Tao
authors: Jie
authors: J
authors: Jin
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D019175:DNA Methylation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000276:immunology*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011467:Prostate / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000276:immunology
chemical_list: C119064:DLEC1 protein, human; D016328:NF-kappa B; D025521:Tumor Suppressor Proteins
references: Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12353-8
references: 17640920
references: J Hepatol. 2008 Mar;48(3):433-41
references: 18191269
references: Oncogene. 2004 Mar 18;23(12):2241-9
references: 14691453
references: Eur Urol. 2011 Oct;60(4):753-66
references: 21719191
references: Cell. 2007 Feb 23;128(4):683-92
references: 17320506
references: BJU Int. 2014 Aug;114(2):168-76
references: 24215139
references: Neoplasia. 2006 Apr;8(4):268-78
references: 16756719
references: Oncogene. 2007 Nov 15;26(52):7283-301
references: 17533367
references: Proc Am Thorac Soc. 2012 May;9(2):64-5
references: 22550245
references: Biomark Cancer. 2010 Feb 18;2:17-33
references: 24179382
references: J Virol. 1998 Sep;72(9):7075-83
references: 9696800
references: Eur Urol. 2004 Nov;46(5):660-9; discussion 669
references: 15474280
references: Clin Cancer Res. 2012 May 15;18(10):2882-95
references: 22589488
references: Oncogene. 1999 Feb 11;18(6):1313-24
references: 10022813
references: J Biol Chem. 2012 Oct 26;287(44):37570-82
references: 22955280
references: Eur Urol. 2003 Jul;44(1):8-15; discussion 15-6
references: 12814669
references: Br J Cancer. 2012 Oct 23;107(9):1554-63
references: 23093296
references: Int J Cancer. 2005 Aug 20;116(2):174-81
references: 15800905
references: CA Cancer J Clin. 2013 Jan;63(1):11-30
references: 23335087
references: Br J Cancer. 2009 Feb 24;100(4):663-9
references: 19156137
references: Anticancer Res. 2010 Apr;30(4):1079-82
references: 20530412
references: Nat Genet. 2012 May 20;44(6):685-9
references: 22610119
references: Am J Pathol. 2009 Aug;175(2):489-99
references: 19628766
references: J Mol Med (Berl). 2013 Nov;91(11):1249-56
references: 24057814
references: Cancer Res. 1999 Apr 15;59(8):1966-72
references: 10213508
references: Expert Rev Mol Diagn. 2009 Apr;9(3):243-57
references: 19379083
references: J Urol. 2013 Feb;189(2):422-9
references: 23017522
references: Am J Pathol. 1999 Aug;155(2):619-25
references: 10433954
references: Br J Cancer. 2008 Jul 22;99(2):375-82
references: 18594535
references: J Urol. 2010 Aug;184(2):731-7
references: 20639048
references: Cancer Res. 2002 Jun 15;62(12):3498-502
references: 12067994
references: Cancer Res. 2004 Mar 15;64(6):1975-86
references: 15026333
references: Clin Cancer Res. 2001 Sep;7(9):2727-30
references: 11555585
references: J Biol Chem. 2012 Nov 16;287(47):39954-66
references: 23012352