{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:34:10Z","timestamp":1789450450122,"version":"build-2803163510"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81372238"],"award-info":[{"award-number":["81372238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["31171243"],"award-info":[{"award-number":["31171243"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81372898"],"award-info":[{"award-number":["81372898"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81172582"],"award-info":[{"award-number":["81172582"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["31420103915"],"award-info":[{"award-number":["31420103915"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"International S&T Cooperation Program of China (ISTCP)","award":["2012DFA10650"],"award-info":[{"award-number":["2012DFA10650"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies suggest that paired box 5 (<jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5) is down\u2010regulated in multiple tumours through its promoter methylation. However, the role of <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 in non\u2010small cell lung cancer (<jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>) pathogenesis remains unclear. The aim of this study is to examine <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 expression, its methylation status, biological functions and related molecular mechanism in <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>. We found that <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 was widely expressed in normal adult tissues but silenced or down\u2010regulated in 88% (7\/8) of <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content> cell lines. <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 expression level was significantly lower in <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content> than that in adjacent non\u2010cancerous tissues (<jats:italic>P<\/jats:italic> = 0.0201). <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 down\u2010regulation was closely associated with its promoter hypermethylation status and <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 expression could be restored by demethylation treatment. Frequent <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 promoter methylation in primary tumours (70%) was correlated with lung tumour histological types (<jats:italic>P<\/jats:italic> = 0.006). Ectopic expression of <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 in silenced lung cancer cell lines (A549 and H1975) inhibited their colony formation and cell viability, arrested cell cycle at G2 phase and suppressed cell migration\/invasion as well as tumorigenicity in nude mice. Restoration of <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 expression resulted in the down\u2010regulation of \u03b2\u2010catenin and up\u2010regulation of tissue inhibitors of metalloproteinase 2, <jats:styled-content style=\"fixed-case\">GADD<\/jats:styled-content>45G in lung tumour cells. In summary, <jats:styled-content style=\"fixed-case\">PAX<\/jats:styled-content>5 was found to be an epigenetically inactivated tumour suppressor that inhibits <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content> cell proliferation and metastasis, through down\u2010regulating the \u03b2\u2010catenin pathway and up\u2010regulating <jats:styled-content style=\"fixed-case\">GADD<\/jats:styled-content>45G expression.<\/jats:p>","DOI":"10.1111\/jcmm.12768","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T11:08:33Z","timestamp":1454584113000},"page":"842-854","source":"Crossref","is-referenced-by-count":20,"title":["Paired box 5 is a frequently methylated lung cancer tumour suppressor gene interfering \u03b2\u2010catenin signalling and <scp>GADD<\/scp>45G expression"],"prefix":"10.1111","volume":"20","author":[{"given":"Lijuan","family":"Zhao","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuman","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Gan","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixiao","family":"Feng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisheng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy Cancer Center Qilu Hospital Shandong University Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Li","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics Laboratory Department of Clinical Oncology Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong and CUHK Shenzhen Research Institute Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Cancer Epigenetics Laboratory Department of Clinical Oncology Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong and CUHK Shenzhen Research Institute Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Peng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can","family":"Xu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianli","family":"Hui","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guosheng","family":"Ren","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Tao","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"},{"name":"Cancer Epigenetics Laboratory Department of Clinical Oncology Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences The Chinese University of Hong Kong and CUHK Shenzhen Research Institute Hong Kong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingxiu","family":"Xiang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory of Molecular Oncology and Epigenetics The First Affiliated Hospital of Chongqing Medical University Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,4]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21254"},{"key":"e_1_2_9_3_1","first-page":"3986","article-title":"Akt\/protein kinase B is constitutively active in non\u2010small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation","volume":"61","author":"Brognard J","year":"2001","journal-title":"Cancer Res"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2013.12.008"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001551200"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0493-292"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.21.3396"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.4.476"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.6.9.1589"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.4.5.849"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2011.511"},{"key":"e_1_2_9_12_1","first-page":"1003","article-title":"Overexpression of PAX5 in oral carcinogenesis","volume":"16","author":"Norhany S","year":"2006","journal-title":"Oncol Rep"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025652203472"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.168"},{"key":"e_1_2_9_15_1","first-page":"4620","article-title":"Aberrant promoter methylation of the transcription factor genes PAX5 alpha and beta in human cancers","volume":"63","author":"Palmisano WA","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20532"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-1874"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24124"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2930"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2009.01.007"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/77083"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231490898"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevOncog.v13.i2.10"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djt356"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000284200"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.10140"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202667"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03032599"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2004.09.006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.pcan.4500750"},{"key":"e_1_2_9_31_1","first-page":"1601","article-title":"Inhibition of cell motility and invasion by HangAmDan\u2010B in NCI\u2010H460 human non\u2010small cell lung cancer cells","volume":"26","author":"Choi YJ","year":"2011","journal-title":"Oncol Rep"},{"key":"e_1_2_9_32_1","first-page":"4833","article-title":"Suppression of cell invasion and migration by propofol are involved in down\u2010regulating matrix metalloproteinase\u20102 and p38 MAPK signaling in A549 human lung adenocarcinoma epithelial cells","volume":"32","author":"Wu KC","year":"2012","journal-title":"Anticancer Res"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000041433.94868.12"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.12768","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.12768","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.12768","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.12768","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T10:21:50Z","timestamp":1713954110000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.12768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,4]]},"references-count":32,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["10.1111\/jcmm.12768"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.12768","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,4]]}}}