MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription
Abstract Background The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our res...
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BMC
2024-01-01
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Series: | Cellular & Molecular Biology Letters |
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Online Access: | https://doi.org/10.1186/s11658-023-00522-0 |
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author | Ying Liang Xin Wei Peng-Jie Yue He-Cheng Zhang Zhen-Ning Li Xiao-Xue Wang Yuan-Yuan Sun Wei-Neng Fu |
author_facet | Ying Liang Xin Wei Peng-Jie Yue He-Cheng Zhang Zhen-Ning Li Xiao-Xue Wang Yuan-Yuan Sun Wei-Neng Fu |
author_sort | Ying Liang |
collection | DOAJ |
description | Abstract Background The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. Methods R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. Results MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. Conclusion This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma. |
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spelling | doaj.art-030f8da311c54c87b297a4fe0a751cd92024-01-07T12:35:45ZengBMCCellular & Molecular Biology Letters1689-13922024-01-0129112010.1186/s11658-023-00522-0MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcriptionYing Liang0Xin Wei1Peng-Jie Yue2He-Cheng Zhang3Zhen-Ning Li4Xiao-Xue Wang5Yuan-Yuan Sun6Wei-Neng Fu7Department of Medical Genetics, China Medical UniversityDepartment of Hematology, The First Affiliated Hospital of China Medical UniversityDepartment of Hematology, The First Affiliated Hospital of China Medical UniversityDepartment of Medical Genetics, China Medical UniversityDepartment of Oromaxillofacial-Head and Neck Surgery, Liaoning Province Key Laboratory of Oral Disease, School and Hospital of Stomatology, China Medical UniversityDepartment of Hematology, The First Affiliated Hospital of China Medical UniversityDepartment of Medical Genetics, China Medical UniversityDepartment of Medical Genetics, China Medical UniversityAbstract Background The abnormality of chromosomal karyotype is one factor causing poor prognosis of lymphoma. In the analysis of abnormal karyotype of lymphoma patients, three smallest overlap regions were found, in which MYCT1 was located. MYCT1 is the first tumor suppressor gene cloned by our research team, but its studies relating to the occurrence and development of lymphoma have not been reported. Methods R banding analyses were employed to screen the abnormality of chromosomal karyotype in clinical specimen and MYCT1 over-expression cell lines. FISH was to monitor MYCT1 copy number aberration. RT-PCR and Western blot were to detect the mRNA and protein levels of the MYCT1 and RUNX1 genes, respectively. The MYCT1 and RUNX1 protein levels in clinical specimen were evaluated by immunohistochemical DAB staining. The interaction between MYCT1 and MAX proteins was identified via Co-IP and IF. The binding of MAX on the promoter of the RUNX1 gene was detected by ChIP and Dual-luciferase reporter assay, respectively. Flow cytometry and CCK-8 assay were to explore the effects of MYCT1 and RUNX1 on the cell cycle and proliferation, respectively. Results MYCT1 was located in one of three smallest overlap regions of diffuse large B-cell lymphoma, it altered chromosomal instability of diffuse large B-cell lymphoma cells. MYCT1 negatively correlated with RUNX1 in lymphoma tissues of the patients. MAX directly promoted the RUNX1 gene transcription by binding to its promoter region. MYCT1 may represses RUNX1 transcription by binding MAX in diffuse large B-cell lymphoma cells. MYCT1 binding to MAX probably suppressed RUNX1 transcription, leading to the inhibition of proliferation and cell cycle of the diffuse large B-cell lymphoma cells. Conclusion This study finds that there is a MYCT1-MAX-RUNX1 signaling pathway in diffuse large B-cell lymphoma. And the study provides clues and basis for the in-depth studies of MYCT1 in the diagnosis, treatment and prognosis of lymphoma.https://doi.org/10.1186/s11658-023-00522-0MYCT1Diffuse large B-cell lymphomaChromosomal karyotype |
spellingShingle | Ying Liang Xin Wei Peng-Jie Yue He-Cheng Zhang Zhen-Ning Li Xiao-Xue Wang Yuan-Yuan Sun Wei-Neng Fu MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription Cellular & Molecular Biology Letters MYCT1 Diffuse large B-cell lymphoma Chromosomal karyotype |
title | MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription |
title_full | MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription |
title_fullStr | MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription |
title_full_unstemmed | MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription |
title_short | MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription |
title_sort | myct1 inhibits hematopoiesis in diffuse large b cell lymphoma by suppressing runx1 transcription |
topic | MYCT1 Diffuse large B-cell lymphoma Chromosomal karyotype |
url | https://doi.org/10.1186/s11658-023-00522-0 |
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