更新于：2024-11-01

c-Myc x RUNX1 x MAX

更新于：2024-11-01

基本信息

关联

项与 c-Myc x RUNX1 x MAX 相关的药物

MYCi361

靶点

MAX x RUNX1 x c-Myc

作用机制

MAX modulators [+2]

在研机构

Hannover Medical School

原研机构

Hannover Medical School

在研适应症

髓系白血病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 c-Myc x RUNX1 x MAX 相关的临床结果

登录后查看更多信息

100 项与 c-Myc x RUNX1 x MAX 相关的转化医学

登录后查看更多信息

0 项与 c-Myc x RUNX1 x MAX 相关的专利（医药）

登录后查看更多信息

项与 c-Myc x RUNX1 x MAX 相关的文献（医药）

2023-03-09·Blood

RUNX1 isoform disequilibrium promotes the development of trisomy 21–associated myeloid leukemia

Article

作者: Ihling, Christian ; Yaspo, Marie-Laure ; Schuschel, Konstantin ; Kadel, Sofie-Katrin ; Ng, Michelle ; Labuhn, Maurice ; Verboon, Lonneke ; Heckl, Dirk ; Laszig, Stephanie ; Glaß, Markus ; Reinhardt, Dirk ; Gialesaki, Sofia ; Alejo-Valle, Oriol ; Hüttelmaier, Stefan ; Klusmann, Jan-Henning ; Regényi, Enikő ; Winkler, Robert ; Sinz, Andrea ; Bräuer-Hartmann, Daniela ; Matzk, Sören ; Strüwe, Farina Josepha ; Bhayadia, Raj ; Schmid, Lena ; Issa, Hasan ; Schmell, Anna-Lena

AbstractGain of chromosome 21 (Hsa21) is among the most frequent aneuploidies in leukemia. However, it remains unclear how partial or complete amplifications of Hsa21 promote leukemogenesis and why children with Down syndrome (DS) (ie, trisomy 21) are particularly at risk of leukemia development. Here, we propose that RUNX1 isoform disequilibrium with RUNX1A bias is key to DS-associated myeloid leukemia (ML-DS). Starting with Hsa21-focused CRISPR–CRISPR-associated protein 9 screens, we uncovered a strong and specific RUNX1 dependency in ML-DS cells. Expression of the RUNX1A isoform is elevated in patients with ML-DS, and mechanistic studies using murine ML-DS models and patient-derived xenografts revealed that excess RUNX1A synergizes with the pathognomonic Gata1s mutation during leukemogenesis by displacing RUNX1C from its endogenous binding sites and inducing oncogenic programs in complex with the MYC cofactor MAX. These effects were reversed by restoring the RUNX1A:RUNX1C equilibrium in patient-derived xenografts in vitro and in vivo. Moreover, pharmacological interference with MYC:MAX dimerization using MYCi361 exerted strong antileukemic effects. Thus, our study highlights the importance of alternative splicing in leukemogenesis, even on a background of aneuploidy, and paves the way for the development of specific and targeted therapies for ML-DS, as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.

2020-12-01·Respiratory Research2区 · 医学

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses

2区 · 医学

ArticleOA

作者: Chen, Wen-Jie ; Gan, Ting-Qing ; Shi, Ke ; Feng, Zhen-Bo ; Li, Zu-Yun ; Gan, Bin-Liang ; Chen, Gang ; Fang, Ye-Ying ; Liang, Chang-Yu ; Dang, Yi-Wu

AbstractBackgroundPulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC).MethodsExpression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references.ResultsThe expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation.ConclusionsThe frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p.