Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma
Abstract Background Epigenetic reprogramming is involved in multiple steps of human cancer evolution and is mediated by a variety of chromatin-modifying enzymes. Specifically, the histone lysine methyltransferase KMT2D is among the most frequently mutated genes in oral squamous cell carcinoma (OSCC)...
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| Format: | Article |
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BMC
2022-04-01
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| Series: | Cell & Bioscience |
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| Online Access: | https://doi.org/10.1186/s13578-022-00785-8 |
| _version_ | 1817982325192916992 |
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| author | Xinmiao Wang Rui Li Luping Wu Yang Chen Shaopeng Liu Hui Zhao Yifan Wang Lin Wang Zhe Shao |
| author_facet | Xinmiao Wang Rui Li Luping Wu Yang Chen Shaopeng Liu Hui Zhao Yifan Wang Lin Wang Zhe Shao |
| author_sort | Xinmiao Wang |
| collection | DOAJ |
| description | Abstract Background Epigenetic reprogramming is involved in multiple steps of human cancer evolution and is mediated by a variety of chromatin-modifying enzymes. Specifically, the histone lysine methyltransferase KMT2D is among the most frequently mutated genes in oral squamous cell carcinoma (OSCC). However, the mechanisms by which KMT2D affects the development of OSCC remain unclear. Results In the present study, we found that the expression of KMT2D was elevated in OSCC compared to paracancerous specimens and was correlated with a more advanced tumor grade. More importantly, knockdown of KMT2D impaired their reconstitution in patient-derived organoids and decreased the expression of CD133 and β-catenin in OSCC cells. In in vitro and in vivo models, knockdown of KMT2D reduced the colony formation, migration and invasion abilities of OSCC cells and delayed tumor growth. Mechanistically, the dual-luciferase reporter and co-immunoprecipitation assays in two individual OSCC cell lines indicated that KMT2D may cooperate with MEF2A to promote the transcription activity of CTNNB1, thereby enhancing WNT signaling. Conclusion The upregulation of KMT2D contributes to stem-like properties in OSCC cells by sustaining the MEF2A-mediated transcriptional activity of CTNNB1. |
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| issn | 2045-3701 |
| language | English |
| last_indexed | 2024-04-13T23:19:23Z |
| publishDate | 2022-04-01 |
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| spelling | doaj.art-443d4463a66f46c5b0edb93b6f209a9a2022-12-22T02:25:18ZengBMCCell & Bioscience2045-37012022-04-0112111310.1186/s13578-022-00785-8Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinomaXinmiao Wang0Rui Li1Luping Wu2Yang Chen3Shaopeng Liu4Hui Zhao5Yifan Wang6Lin Wang7Zhe Shao8The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityDepartment of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan UniversityAbstract Background Epigenetic reprogramming is involved in multiple steps of human cancer evolution and is mediated by a variety of chromatin-modifying enzymes. Specifically, the histone lysine methyltransferase KMT2D is among the most frequently mutated genes in oral squamous cell carcinoma (OSCC). However, the mechanisms by which KMT2D affects the development of OSCC remain unclear. Results In the present study, we found that the expression of KMT2D was elevated in OSCC compared to paracancerous specimens and was correlated with a more advanced tumor grade. More importantly, knockdown of KMT2D impaired their reconstitution in patient-derived organoids and decreased the expression of CD133 and β-catenin in OSCC cells. In in vitro and in vivo models, knockdown of KMT2D reduced the colony formation, migration and invasion abilities of OSCC cells and delayed tumor growth. Mechanistically, the dual-luciferase reporter and co-immunoprecipitation assays in two individual OSCC cell lines indicated that KMT2D may cooperate with MEF2A to promote the transcription activity of CTNNB1, thereby enhancing WNT signaling. Conclusion The upregulation of KMT2D contributes to stem-like properties in OSCC cells by sustaining the MEF2A-mediated transcriptional activity of CTNNB1.https://doi.org/10.1186/s13578-022-00785-8KMT2DMEF2AStemnessOSCCCTNNB1Organoid |
| spellingShingle | Xinmiao Wang Rui Li Luping Wu Yang Chen Shaopeng Liu Hui Zhao Yifan Wang Lin Wang Zhe Shao Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma Cell & Bioscience KMT2D MEF2A Stemness OSCC CTNNB1 Organoid |
| title | Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma |
| title_full | Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma |
| title_fullStr | Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma |
| title_full_unstemmed | Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma |
| title_short | Histone methyltransferase KMT2D cooperates with MEF2A to promote the stem-like properties of oral squamous cell carcinoma |
| title_sort | histone methyltransferase kmt2d cooperates with mef2a to promote the stem like properties of oral squamous cell carcinoma |
| topic | KMT2D MEF2A Stemness OSCC CTNNB1 Organoid |
| url | https://doi.org/10.1186/s13578-022-00785-8 |
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