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. 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. 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. 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.

中文翻译：

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MYCT1 通过抑制 RUNX1 转录来抑制弥漫性大 B 细胞淋巴瘤的造血

染色体核型异常是淋巴瘤预后不良的因素之一。在对淋巴瘤患者的异常核型分析中，发现了三个最小的重叠区域，其中MYCT1位于其中。MYCT1是我们课题组克隆的第一个抑癌基因，但其与淋巴瘤发生、发展相关的研究尚未见报道。采用R显带分析方法筛选临床标本和MYCT1过表达细胞系的染色体核型异常情况。FISH 用于监测 MYCT1 拷贝数畸变。RT-PCR和Western blot分别检测MYCT1和RUNX1基因的mRNA和蛋白水平。通过免疫组化DAB染色评估临床标本中MYCT1和RUNX1蛋白水平。通过 Co-IP 和 IF 鉴定了 MYCT1 和 MAX 蛋白之间的相互作用。分别通过 ChIP 和双荧光素酶报告基因测定检测 MAX 在 RUNX1 基因启动子上的结合。流式细胞术和CCK-8实验分别探讨MYCT1和RUNX1对细胞周期和增殖的影响。MYCT1位于弥漫性大B细胞淋巴瘤的三个最小重叠区域之一，它改变了弥漫性大B细胞淋巴瘤细胞的染色体不稳定性。患者淋巴瘤组织中MYCT1与RUNX1呈负相关。MAX通过结合RUNX1基因的启动子区域直接促进RUNX1基因转录。MYCT1 可能通过在弥漫性大 B 细胞淋巴瘤细胞中结合 MAX 来抑制 RUNX1 转录。MYCT1 与 MAX 结合可能抑制 RUNX1 转录，从而抑制弥漫性大 B 细胞淋巴瘤细胞的增殖和细胞周期。本研究发现弥漫性大B细胞淋巴瘤中存在MYCT1-MAX-RUNX1信号通路。该研究为深入研究MYCT1在淋巴瘤的诊断、治疗和预后中的作用提供了线索和依据。