{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:25:12Z","timestamp":1788449112256,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,12,2]],"date-time":"2019-12-02T00:00:00Z","timestamp":1575244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470736"],"award-info":[{"award-number":["81470736"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Oral squamous cell carcinoma (OSCC) is usually diagnosed at late stages, which leads to high morbidity. There are evidence that chronic inflammation (eg oral lichen planus [OLP]) was a risk factor of OSCC, but often misdiagnosed or ignored until invasion and metastasis. By applying precision medicine, the molecular microenvironment variations and relevant biomarkers for the malignant transformation from OLP to OSCC can be fully investigated. Several studies pointed out that the metabolic pathway were suppressed in OSCC. However, it remains unclear how the systemic profile of the metabolites change during the malignant transformation. In this study, we examined and compared the mucosa samples from 11 healthy individuals, 10 OLP patients and 21 OSCC patients. Based on the results, succinate, a key metabolite of the tricarboxylic acid cycle pathway, was accumulated in the primary cultured precancerous OLP keratinocytes and OSCC cells. Then, we found that succinate activated the hypoxia\u2010inducible factor\u20101 alpha (HIF\u20101\u03b1) pathway and induced apoptosis, which could also be up\u2010regulated by the tumour suppressor lncRNA MEG3. These results suggested the critical roles of succinate and MEG3 in the metabolic changes during malignant transformation from OLP to OSCC, which indicated that succinate, HIF1\u03b1 and downstream proteins might serve as new biomarkers of precancerous OLP for early diagnosis and therapeutic monitoring. In addition, succinate or its prodrugs might become a potential therapy for the prevention or treatment of OSCC.<\/jats:p>","DOI":"10.1111\/jcmm.14376","type":"journal-article","created":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T03:04:17Z","timestamp":1575342257000},"page":"1179-1188","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Metabolic changes during malignant transformation in primary cells of oral lichen planus: Succinate accumulation and tumour suppression"],"prefix":"10.1111","volume":"24","author":[{"given":"Qiaozhen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Stomatology Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4689-7592","authenticated-orcid":false,"given":"Hongying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Stomatology Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuedi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Stomatology Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Stomatology Huashan Hospital, Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiyin","family":"Hexige","sequence":"additional","affiliation":[{"name":"School of Life Sciences Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2014.2103"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604633"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2003.08.001"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2013.04.004"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000007012"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tripleo.2010.11.007"},{"key":"e_1_2_8_8_1","first-page":"1947","article-title":"Salivary MMP\u20101, MMP\u20102, MMP\u20103 and MMP\u201013 levels in patients with oral lichen planus and squamous cell carcinoma","volume":"18","author":"Nosratzehi T","year":"2017","journal-title":"Asian Pac J Cancer Prev"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2017.06.006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4420"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11706"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4145"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2017.5487"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2014.04.003"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac9709458"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2006.05.023"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/152308603768295212"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6927328"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.14715\/cmb\/2016.62.14.11"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-012-0906-3"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-12-0008"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3611"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973-1482.176414"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oooo.2013.01.022"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14376","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.14376","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T15:00:17Z","timestamp":1788447617000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.14376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,2]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2020,1]]}},"alternative-id":["10.1111\/jcmm.14376"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.14376","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,2]]},"assertion":[{"value":"2019-01-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}