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MYCT1 inhibits hematopoiesis in diffuse large B-cell lymphoma by suppressing RUNX1 transcription
Ying Liang1,2, Xin Wei2, Peng-Jie Yue2
1Department of Medical Genetics, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning Province, 110122, People's Republic of China.
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.
Insights
The MYCT1 tumor suppressor gene impacts diffuse large B-cell lymphoma by inhibiting the MYCT1-MAX-RUNX1 pathway, affecting cell proliferation and cell cycle. This discovery offers new insights for lymphoma diagnosis and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosomal abnormalities are linked to poor lymphoma prognosis.
- MYCT1, a tumor suppressor gene, was identified in critical regions of lymphoma karyotypes.
- The role of MYCT1 in lymphoma development was previously uninvestigated.
Purpose of the Study:
- To investigate the role of the MYCT1 gene in the context of lymphoma.
- To elucidate the molecular mechanisms involving MYCT1 in diffuse large B-cell lymphoma (DLBCL).
- To identify potential therapeutic targets within the MYCT1 signaling pathway.
Main Methods:
- Karyotype analysis, FISH, RT-PCR, and Western blotting were used to assess chromosomal and gene expression changes.
- Immunohistochemistry evaluated MYCT1 and RUNX1 protein levels in patient tissues.
- Co-IP, IF, ChIP, and dual-luciferase assays investigated protein interactions and gene regulation.
- Flow cytometry and CCK-8 assays assessed cell cycle and proliferation effects.
Main Results:
- MYCT1 is located in a key region in DLBCL and influences chromosomal instability.
- A negative correlation was observed between MYCT1 and RUNX1 expression in lymphoma tissues.
- The MAX protein directly upregulates RUNX1 transcription, while MYCT1 binding to MAX appears to repress RUNX1.
- MYCT1-MAX interaction suppresses RUNX1 transcription, inhibiting DLBCL cell proliferation and cell cycle progression.
Conclusions:
- A novel MYCT1-MAX-RUNX1 signaling pathway was identified in DLBCL.
- This pathway plays a crucial role in regulating cell proliferation and cell cycle in DLBCL.
- Findings provide a foundation for future research into MYCT1's diagnostic, therapeutic, and prognostic potential in lymphoma.
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