{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:04:35Z","timestamp":1789736675873,"version":"4.0.1"},"reference-count":53,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T00:00:00Z","timestamp":1604102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health and Welfare Health and welfare surcharge of tobacco products, Taiwan","award":["MOHW107-TDU-B-212-114013, MOHW109-TDU-B-212-134016"],"award-info":[{"award-number":["MOHW107-TDU-B-212-114013, MOHW109-TDU-B-212-134016"]}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["109-2314-B-006-013 -, 109-2740-B-400-002-, 108-2314-B-006-018-, 106-2314-B-006-016-, 104-2314-B-006-062-"],"award-info":[{"award-number":["109-2314-B-006-013 -, 109-2740-B-400-002-, 108-2314-B-006-018-, 106-2314-B-006-016-, 104-2314-B-006-062-"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Health Research Institutes, Taiwan","award":["CA-109-PP-18"],"award-info":[{"award-number":["CA-109-PP-18"]}]},{"DOI":"10.13039\/501100004844","name":"National Cheng Kung University Hospital","doi-asserted-by":"publisher","award":["NCKUH-10902064, NCKUH-10604032, NCKUH-10406031"],"award-info":[{"award-number":["NCKUH-10902064, NCKUH-10604032, NCKUH-10406031"]}],"id":[{"id":"10.13039\/501100004844","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Higher Education Sprout Project, Ministry of Education to the Headquarters of University Advancement at National Cheng Kung University","award":["NCKU"],"award-info":[{"award-number":["NCKU"]}]},{"name":"Chi-Mei Medical Center, Liouying","award":["CMNCKU10517, CMNCKU10602, CLFHR10801"],"award-info":[{"award-number":["CMNCKU10517, CMNCKU10602, CLFHR10801"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Oral carcinogenesis involves the progression of the normal mucosa into potentially malignant disorders and finally into cancer. Tumors are heterogeneous, with different clusters of cells expressing different genes and exhibiting different behaviors. 4-nitroquinoline 1-oxide (4-NQO) and arecoline were used to induce oral cancer in mice, and the main factors for gene expression influencing carcinogenesis were identified through single-cell RNA sequencing analysis. Male C57BL\/6J mice were divided into two groups: a control group (receiving normal drinking water) and treatment group (receiving drinking water containing 4-NQO (200 mg\/L) and arecoline (500 mg\/L)) to induce the malignant development of oral cancer. Mice were sacrificed at 8, 16, 20, and 29 weeks. Except for mice sacrificed at 8 weeks, all mice were treated for 16 weeks and then either sacrificed or given normal drinking water for the remaining weeks. Tongue lesions were excised, and all cells obtained from mice in the 29- and 16-week treatment groups were clustered into 17 groups by using the Louvain algorithm. Cells in subtypes 7 (stem cells) and 9 (keratinocytes) were analyzed through gene set enrichment analysis. Results indicated that their genes were associated with the MYC_targets_v1 pathway, and this finding was confirmed by the presence of cisplatin-resistant nasopharyngeal carcinoma cell lines. These cell subtype biomarkers can be applied for the detection of patients with precancerous lesions, the identification of high-risk populations, and as a treatment target.<\/jats:p>","DOI":"10.3390\/ijms21218171","type":"journal-article","created":{"date-parts":[[2020,10,31]],"date-time":"2020-10-31T21:39:56Z","timestamp":1604180396000},"page":"8171","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model"],"prefix":"10.3390","volume":"21","author":[{"given":"Ling-Yu","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5139-3612","authenticated-orcid":false,"given":"Daw-Yang","family":"Hwang","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih Sheng","family":"Jiang","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Tsung","family":"Huang","sequence":"additional","affiliation":[{"name":"Chi Mei Medical Center, Liouying, Tainan 73659, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Fan","family":"Chiang","sequence":"additional","affiliation":[{"name":"Chi Mei Medical Center, Liouying, Tainan 73659, Taiwan"},{"name":"School of Dentistry, National Yang Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko-Jiunn","family":"Liu","sequence":"additional","affiliation":[{"name":"National Institute of Cancer Research, National Health Research Institutes, Tainan 70456, Taiwan"},{"name":"Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807377, Taiwan"},{"name":"Institute of Clinical Pharmacy and Pharmaceutical Sciences and Institute of Clinical Medicine, National Cheng Kung University, Tainan 704302, Taiwan"},{"name":"School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tze-Ta","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Oral Medicine, Department of Dentistry, Division of Oral and Maxillofacial Surgery, Department of Stomatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lousada-Fernandez, F., Rapado-Gonzalez, O., Lopez-Cedrun, J.L., Lopez-Lopez, R., Muinelo-Romay, L., and Suarez-Cunqueiro, M.M. 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