caa a22 4500 605542910 CHVBK 20210128100924.0 cr unu---uuuuu 210128e20150601xx s 000 0 eng 10.1007/s00109-015-1255-5 doi (NATIONALLICENCE)springer-10.1007/s00109-015-1255-5 DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer [Elektronische Daten] [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] 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. Springer-Verlag Berlin Heidelberg, 2015 DLEC1 nationallicence Prostate cancer nationallicence Tumor suppressor gene nationallicence Methylation nationallicence NF-κB nationallicence Aza : 5-Aza-2-deoxycytidine nationallicence ATCC : The American Type Culture Collection nationallicence BGS : Bisulfite genomic sequence nationallicence BPH : Benign prostatic hyperplasia nationallicence DLEC1 : Deleted in lung and esophageal cancer nationallicence DRE : Digital rectal examination nationallicence FBS : Fetal bovine serum nationallicence IHC : Immunohistochemistry nationallicence MSP : Methylation specific polymerase chain reaction nationallicence PrCa : Prostate cancer nationallicence RT-PCR : Reverse-transcription polymerase chain reaction nationallicence RP : Radical prostatectomy nationallicence TSA : Trichostatin A nationallicence TSG : Tumor suppressor gene nationallicence TUR : Transurethral resection nationallicence Zhang Lian Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Zhang Qian Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Li LiLi 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 aut Wang Zhaohui 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 aut Ying Jianming Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China aut Fan Yu Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut He Qun Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut LV Tianjing Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Han Wenke Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Li Jun Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Yang Yang Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Xu Ben Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Wang Lu Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Liu Qianling Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Sun Yinghao Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China aut Guo Yinglu Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Tao Qian 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 aut Jin Jie Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut Journal of Molecular Medicine Springer Berlin Heidelberg 93/6(2015-06-01), 691-701 0946-2716 93:6<691 2015 93 109 https://doi.org/10.1007/s00109-015-1255-5 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00109-015-1255-5 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Lian Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Zhang Qian Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Li LiLi 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 aut NATIONALLICENCE 700 1- Wang Zhaohui 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 aut NATIONALLICENCE 700 1- Ying Jianming Department of Pathology, Cancer Institute and Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China aut NATIONALLICENCE 700 1- Fan Yu Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- He Qun Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- LV Tianjing Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Han Wenke Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Li Jun Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Yang Yang Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Xu Ben Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Wang Lu Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Liu Qianling Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Sun Yinghao Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China aut NATIONALLICENCE 700 1- Guo Yinglu Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 700 1- Tao Qian 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 aut NATIONALLICENCE 700 1- Jin Jie Department of Urology, National Research Center for Genitourinary Oncology, Peking University First Hospital and Institute of Urology, Beijing, China aut NATIONALLICENCE 773 0- Journal of Molecular Medicine Springer Berlin Heidelberg 93/6(2015-06-01), 691-701 0946-2716 93:6<691 2015 93 109