TCF21的SUMO化修饰在乳腺癌相关雌激素信号通路中的调控作用

TCF21 is the member of bHLH family, which play roles in the development of cardiovascular, genital and gastrointestinal system. The previous study showed that the hyper-methylation in the promoter of TCF21 has been identified in malignancy tumors, but there are very few studies on the mechanism of TCF21 in the roles of tumors. In our preliminary studies, TCF21 showed lower expressions in breast cancer tissues compared with the normal tissues. Our data also showed that TCF21 can interacted with estrogen receptor ERα, showing that TCF21may participate in the molecular regulation of estrogen receptor signal pathway. SUMOylation is an important modification of protein post-translation, which takes crucial effects in regulating the activity, stability and association of proteins. Based on our preliminary data, TCF21 could be SUMOylated and SUMOylation of TCF21 promoted its stability. The further study will not only discover the gene transcription network of nuclear receptor, but it will do a favor to understanding the regulation mechanism of the SUMOylation of transcription related factors in the process of breast tumorgenesis and development, and these will provide the important theoretical basis for the prevention and therapy of breast cancer.

TCF21作为bHLH家族成员，在调控心血管、生殖和胃肠系统的发育过程中发挥重要作用。有研究发现，在多种恶性肿瘤中TCF21启动子的异常甲基化而使其处于失活状态，但对于TCF21在肿瘤中的作用机制研究还很少。我们初步研究发现，与正常乳腺组织相比，TCF21在乳腺癌组织中呈现低表达，且发现TCF21可以与雌激素受体ERα发生相互作用，这表明TCF21可能参与了雌激素信号通路的分子调控。同时，SUMO化作为一种蛋白质翻译后的重要修饰方式，在调控蛋白质的活性、稳定性、相互作用等方面发挥重要作用。基于我们前期研究发现，TCF21可以被SUMO化修饰，且SUMO化能增强其蛋白质稳定性。因此，进一步的研究，不仅可以揭示核受体的基因调控网络，还将有助于我们更好地了解转录相关因子的SUMO化修饰在乳腺癌发生、发展过程中的分子调控机制，为乳腺癌的预防和治疗提供重要的理论依据。

肿瘤的发生已发展成为一种危害公共健康的恶性疾病，严重威胁着人类的身体健康和家庭的幸福。蛋白质是生理、病理条件下直接的功能分子。蛋白质翻译后修饰是蛋白质动态反应和相互作用的重要分子基础，也是细胞信号网络调控的重要靶点。本项目研究发现了多种与肿瘤发生发展密切相关蛋白的重要翻译后修饰，并对其在肿瘤中的作用机制进行了深入研究。我们的工作首次将蛋白质的翻译后修饰与肿瘤的发生发展联系起来，这将有助于揭示恶性肿瘤发生的精确分子机制，并为恶性肿瘤的治疗和预防提供了理论参考。