A novel tumor suppressing role for RUNX3 is shown where a direct interaction with MYC leads to disruption of MYC-MAX heterodimers and consequent degradation of the MYC oncoprotein

Developmental regulator RUNX3 targets MYC protein for rapid degradation through the glycogen synthase kinase-3 beta-box/WD repeat-containing protein 7 (GSK3β-FBXW7) proteolytic pathway. We therefore uncover a previously unknown mode of MYC destabilization by RUNX3 and provide an explanation as to why RUNX3 inhibits early-stage cancer development in gastrointestinal and lung mouse cancer models. Transcriptional profiling of HeLa-RUNX3 and MKN28-RUNX3 doxycycline inducible cell lines comparing non-treated samples with doxycycline-treatment (RUNX3 induction) samples. The aim of this experiment was to evaluate the functions and effects of RUNX3 induction in these cell lines in vitro. There are three replicates for each condition.

发育调节因子RUNX3可通过糖原合成酶激酶3β盒/WD重复包含蛋白7（GSK3β-FBXW7）蛋白水解通路，靶向MYC蛋白使其快速降解。本研究由此揭示了RUNX3介导MYC蛋白去稳定化的全新机制，并为RUNX3在胃肠道与肺部小鼠癌症模型中抑制肿瘤早期发生的现象提供了合理解释。本研究针对多西环素诱导型细胞系HeLa-RUNX3与MKN28-RUNX3开展转录组谱分析，比较未处理样本与多西环素处理（即RUNX3诱导）样本的基因表达差异。本实验旨在体外评估RUNX3诱导在上述细胞系中所发挥的功能与效应。每组实验条件均设置3次生物学重复。