DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer

Verfasser / Beitragende:
[Lian Zhang, Qian Zhang, LiLi Li, Zhaohui Wang, Jianming Ying, Yu Fan, Qun He, Tianjing LV, Wenke Han, Jun Li, Yang Yang, Ben Xu, Lu Wang, Qianling Liu, Yinghao Sun, Yinglu Guo, Qian Tao, Jie Jin]
Ort, Verlag, Jahr:
2015
Enthalten in:
Journal of Molecular Medicine, 93/6(2015-06-01), 691-701
Format:
Artikel (online)
ID: 605542910
LEADER caa a22 4500
001 605542910
003 CHVBK
005 20210128100924.0
007 cr unu---uuuuu
008 210128e20150601xx s 000 0 eng
024 7 0 |a 10.1007/s00109-015-1255-5  |2 doi 
035 |a (NATIONALLICENCE)springer-10.1007/s00109-015-1255-5 
245 0 0 |a DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer  |h [Elektronische Daten]  |c [Lian Zhang, Qian Zhang, LiLi Li, Zhaohui Wang, Jianming Ying, Yu Fan, Qun He, Tianjing LV, Wenke Han, Jun Li, Yang Yang, Ben Xu, Lu Wang, Qianling Liu, Yinghao Sun, Yinglu Guo, Qian Tao, Jie Jin] 
520 3 |a 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. Key messages: • 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. 
540 |a Springer-Verlag Berlin Heidelberg, 2015 
690 7 |a DLEC1  |2 nationallicence 
690 7 |a Prostate cancer  |2 nationallicence 
690 7 |a Tumor suppressor gene  |2 nationallicence 
690 7 |a Methylation  |2 nationallicence 
690 7 |a NF-κB  |2 nationallicence 
690 7 |a Aza : 5-Aza-2-deoxycytidine  |2 nationallicence 
690 7 |a ATCC : The American Type Culture Collection  |2 nationallicence 
690 7 |a BGS : Bisulfite genomic sequence  |2 nationallicence 
690 7 |a BPH : Benign prostatic hyperplasia  |2 nationallicence 
690 7 |a DLEC1 : Deleted in lung and esophageal cancer  |2 nationallicence 
690 7 |a DRE : Digital rectal examination  |2 nationallicence 
690 7 |a FBS : Fetal bovine serum  |2 nationallicence 
690 7 |a IHC : Immunohistochemistry  |2 nationallicence 
690 7 |a MSP : Methylation specific polymerase chain reaction  |2 nationallicence 
690 7 |a PrCa : Prostate cancer  |2 nationallicence 
690 7 |a RT-PCR : Reverse-transcription polymerase chain reaction  |2 nationallicence 
690 7 |a RP : Radical prostatectomy  |2 nationallicence 
690 7 |a TSA : Trichostatin A  |2 nationallicence 
690 7 |a TSG : Tumor suppressor gene  |2 nationallicence 
690 7 |a TUR : Transurethral resection  |2 nationallicence 
700 1 |a Zhang  |D Lian  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Zhang  |D Qian  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Li  |D LiLi  |u Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shatin, Hong Kong  |4 aut 
700 1 |a Wang  |D Zhaohui  |u Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shatin, Hong Kong  |4 aut 
700 1 |a Ying  |D Jianming  |u Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China  |4 aut 
700 1 |a Fan  |D Yu  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a He  |D Qun  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a LV  |D Tianjing  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Han  |D Wenke  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Li  |D Jun  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Yang  |D Yang  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Xu  |D Ben  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Wang  |D Lu  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Liu  |D Qianling  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Sun  |D Yinghao  |u Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China  |4 aut 
700 1 |a Guo  |D Yinglu  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
700 1 |a Tao  |D Qian  |u Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shatin, Hong Kong  |4 aut 
700 1 |a Jin  |D Jie  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
773 0 |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/6(2015-06-01), 691-701  |x 0946-2716  |q 93:6<691  |1 2015  |2 93  |o 109 
856 4 0 |u https://doi.org/10.1007/s00109-015-1255-5  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00109-015-1255-5  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Lian  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Zhang  |D Qian  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D LiLi  |u Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shatin, Hong Kong  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Zhaohui  |u Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shatin, Hong Kong  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Ying  |D Jianming  |u Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Fan  |D Yu  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a He  |D Qun  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a LV  |D Tianjing  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Han  |D Wenke  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Li  |D Jun  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Yang  |D Yang  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Xu  |D Ben  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Wang  |D Lu  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Liu  |D Qianling  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Sun  |D Yinghao  |u Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Guo  |D Yinglu  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Tao  |D Qian  |u Cancer Epigenetics Laboratory, State Key Laboratory of Oncology in South China, Sir YK Pao Center for Cancer, Department of Clinical Oncology, The Chinese University of Hong Kong and CUHK Shenzhen Research Institute, Shatin, Hong Kong  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Jin  |D Jie  |u Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Journal of Molecular Medicine  |d Springer Berlin Heidelberg  |g 93/6(2015-06-01), 691-701  |x 0946-2716  |q 93:6<691  |1 2015  |2 93  |o 109