{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T12:41:24Z","timestamp":1788871284199,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T00:00:00Z","timestamp":1370995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Basic Research Program of China","doi-asserted-by":"crossref","award":["2010CB833605"],"award-info":[{"award-number":["2010CB833605"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004602","name":"Program for New Century Excellent Talents in University","doi-asserted-by":"crossref","award":["NCET-10-0790"],"award-info":[{"award-number":["NCET-10-0790"]}],"id":[{"id":"10.13039\/501100004602","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["30801322"],"award-info":[{"award-number":["30801322"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81272972"],"award-info":[{"award-number":["81272972"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004761","name":"Provincial Natural Science Foundation of Hunan","doi-asserted-by":"crossref","award":["10JJ4025"],"award-info":[{"award-number":["10JJ4025"]}],"id":[{"id":"10.13039\/501100004761","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Incubation Program for National Natural Science Funds for Distinguished Young Scholar of Central South University","award":["2010QYZD006"],"award-info":[{"award-number":["2010QYZD006"]}]},{"DOI":"10.13039\/501100012588","name":"Open-End Fund for the Valuable and Precision Instruments of Central South University","doi-asserted-by":"crossref","award":["CSUZC2012010"],"award-info":[{"award-number":["CSUZC2012010"]}],"id":[{"id":"10.13039\/501100012588","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012588","name":"Open-End Fund for the Valuable and Precision Instruments of Central South University","doi-asserted-by":"crossref","award":["CSUZC2012009"],"award-info":[{"award-number":["CSUZC2012009"]}],"id":[{"id":"10.13039\/501100012588","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Previous studies have shown that promoter hypermethylation plays a key role in\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      inactivation in nasopharyngeal carcinoma (NPC). However,\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      mutation in NPC has not been reported, and there remain some discrepancies in methods and results between different groups. Here, we examined the mRNA and protein expression of\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      in chronic nasopharyngitis (CN) and NPC tissues by reverse transcription\u2010polymerase chain reaction\/qPCR and immunohistochemistry, respectively.\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      mRNA was undetectable in all the seven widely used NPC cell lines and absent or significantly down\u2010regulated in 70% of NPC tissues. DLC\u20101 protein level was reduced in 74.3% of NPCs when compared with CN tissues, and significantly lower in NPC samples at advanced clinical stages than that at early stages. Then, we purified the same batch of specimens by microdissection and analyzed the possible mechanisms of\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      downregulation with mutation and allelic loss analysis, methylation\u2010specific PCR and bisulfite genomic sequencing. Only one mutation was detected at codon 693 of exon 8 in 3.3% of NPCs and five single nucleotide polymorphisms (SNPs) were identified. Loss of\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      was detected in 23.3% of NPC tissues. The 100% of NPC cell lines, 80% of primary NPC and 22.2% of CN tissues showed methylation in\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      promoter, while\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      expression was recovered in seven NPC cell lines after 5\u2010aza\u2010dC treatment. Patched methylation assay confirmed that promoter methylation could repress\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      expression. This report demonstrates that\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      is negatively associated with NPC carcinogenesis, and promoter hypermethylation along with loss of heterozygosity, but not mutation, contributes to inactivation of\n                      <jats:italic>DLC\u20101<\/jats:italic>\n                      in NPC. \u00a9 2013 Wiley Periodicals, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mc.22044","type":"journal-article","created":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T08:22:38Z","timestamp":1371025358000},"page":"858-870","source":"Crossref","is-referenced-by-count":9,"title":["Promoter hypermethylation along with LOH, but not mutation, contributes to inactivation of\n                    <i>DLC\u20101<\/i>\n                    in nasopharyngeal carcinoma"],"prefix":"10.1002","volume":"53","author":[{"given":"Xiangling","family":"Feng","sequence":"first","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiping","family":"Ren","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Pathology Hunan Tumor Hospital Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifei","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitai","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory for Carcinogenesis of Chinese Ministry of Health, Key Laboratory for Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Cancer Research Institute, Xiangya School of Medicine Central South University Changsha, Hunan, P.R. China"},{"name":"Cancer Research Institute Southern Medical University Guangzhou, Guangdong, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjun","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Xiangya Hospital, Central South University Changsha, Hunan, P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,6,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0b013e3282fad846"},{"key":"e_1_2_6_3_1","first-page":"29","article-title":"Epidemiological trends of nasopharyngeal carcinoma in China","volume":"11","author":"Wei KR","year":"2010","journal-title":"Asian Pac J Cancer Prev"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.010.10377"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399407000312"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2011.12.011"},{"key":"e_1_2_6_7_1","first-page":"2196","article-title":"Cloning, characterization, and chromosomal localization of a gene frequently deleted in human liver cancer (DLC\u20101) homologous to rat RhoGAP","volume":"58","author":"Yuan BZ","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2007.00098.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1672608"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-008-9167-2"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2007.04.008"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2006.00164.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209839"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-009-9184-1"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3727\/000000007783980873"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-011-0673-7"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-11-217"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmn006"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.05217"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65157-7"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.23101"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3727\/000000006783981008","article-title":"Genetic and epigenetic alterations of LTF at 3p21.3 in nasopharyngeal carcinoma","volume":"16","author":"Yi HM","year":"2006","journal-title":"Oncol Res"},{"key":"e_1_2_6_23_1","first-page":"120","article-title":"Laser capture microdissection in the tissue biorepository","volume":"21","author":"Liu A","year":"2010","journal-title":"J Biomol Tech"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207246"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/35101031"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/gte.2007.0121"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2003.12.018"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2004.09.021"},{"key":"e_1_2_6_29_1","first-page":"133","article-title":"DNA variants of DLC\u20101, a candidate tumor suppressor gene in human hepatocellular carcinoma","volume":"23","author":"Park SW","year":"2003","journal-title":"Int J Oncol"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(200002)15:2<156::AID-HUMU4>3.0.CO;2-4"},{"key":"e_1_2_6_31_1","first-page":"7646","article-title":"Genetic and epigenetic alterations of DLC\u20101 gene in hepatocellular carcinoma","volume":"63","author":"Wong CM","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(03)00081-2"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.5732\/cjc.011.10080"},{"key":"e_1_2_6_34_1","first-page":"2039","article-title":"p16 gene alterations in nasopharyngeal carcinoma","volume":"55","author":"Lo KW","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1207632"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10406"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.10.2023"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-08-1245"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgm116"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-380864-6.00001-8"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22044","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmc.22044","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.22044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T21:49:10Z","timestamp":1696369750000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.22044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,12]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2014,11]]}},"alternative-id":["10.1002\/mc.22044"],"URL":"https:\/\/doi.org\/10.1002\/mc.22044","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,12]]}}}