Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model
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 wer...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8171 |
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| author | Ling-Yu Huang Yi-Ping Hsieh Yen-Yun Wang Daw-Yang Hwang Shih Sheng Jiang Wen-Tsung Huang Wei-Fan Chiang Ko-Jiunn Liu Tze-Ta Huang |
| author_facet | Ling-Yu Huang Yi-Ping Hsieh Yen-Yun Wang Daw-Yang Hwang Shih Sheng Jiang Wen-Tsung Huang Wei-Fan Chiang Ko-Jiunn Liu Tze-Ta Huang |
| author_sort | Ling-Yu Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T15:09:54Z |
| format | Article |
| id | doaj.art-8dd6235853634708b5fe53c582907cf5 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:09:54Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8dd6235853634708b5fe53c582907cf52023-11-20T19:25:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121817110.3390/ijms21218171Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse ModelLing-Yu Huang0Yi-Ping Hsieh1Yen-Yun Wang2Daw-Yang Hwang3Shih Sheng Jiang4Wen-Tsung Huang5Wei-Fan Chiang6Ko-Jiunn Liu7Tze-Ta Huang8Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanInstitute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 701401, TaiwanSchool of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung 80708, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanChi Mei Medical Center, Liouying, Tainan 73659, TaiwanChi Mei Medical Center, Liouying, Tainan 73659, TaiwanNational Institute of Cancer Research, National Health Research Institutes, Tainan 70456, TaiwanInstitute 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, TaiwanOral 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.https://www.mdpi.com/1422-0067/21/21/8171mouse modelcarcinogenesissingle-cell RNA sequencingoral cancer |
| spellingShingle | Ling-Yu Huang Yi-Ping Hsieh Yen-Yun Wang Daw-Yang Hwang Shih Sheng Jiang Wen-Tsung Huang Wei-Fan Chiang Ko-Jiunn Liu Tze-Ta Huang Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model International Journal of Molecular Sciences mouse model carcinogenesis single-cell RNA sequencing oral cancer |
| title | Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model |
| title_full | Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model |
| title_fullStr | Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model |
| title_full_unstemmed | Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model |
| title_short | Single-Cell Analysis of Different Stages of Oral Cancer Carcinogenesis in a Mouse Model |
| title_sort | single cell analysis of different stages of oral cancer carcinogenesis in a mouse model |
| topic | mouse model carcinogenesis single-cell RNA sequencing oral cancer |
| url | https://www.mdpi.com/1422-0067/21/21/8171 |
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