TRIM24通过调控NF-κB促进结直肠癌细胞增殖和存活的机制研究

结直肠癌（CRC）是一种常见的致命性疾病，传统化疗药物和靶向治疗药物均存在一定的局限性，新的药物靶点和治疗策略亟待发展。文献报道TRIM24的上调表达与多种肿瘤包括CRC的发展相关，但其在CRC中的致病机制还不明确。我们在预实验中发现TRIM24是维持CRC细胞增殖和存活的关键因子；在CRC细胞系中敲减TRIM24后，NF-κB下游抗凋亡靶基因的mRNA和蛋白水平也随之下调；我们进一步通过免疫共沉淀发现TRIM24可以特异地结合NF-κB家族成员p65。结果提示：TRIM24可能通过结合p65调控NF-κB从而促进CRC细胞增殖和存活。为了证实以上推测，我们将结合多种分子生物学和细胞生物学手段，揭示TRIM24调控NF-κB的分子机制，并在CRC小鼠模型、CRC类器官以及CRC患者肿瘤组织中对其进行验证。本研究旨在揭示TRIM24促进CRC发展的分子机制，为临床治疗提供新的治疗靶点。

Colorectal cancer (CRC) is a common and lethal disease. Both traditional chemotherapy drugs and targeted therapy drugs have certain limitations, and new drug targets and treatment strategies need to be developed urgently. The upregulated expression of TRIM24 has been reported to be associated with the development of a variety of tumors, including CRC, but the pathogenesis of TRIM24 in CRC remains unclear. We found that TRIM24 was a key factor in maintaining the proliferation and survival of CRC cells. Knocking down TRIM24 in CRC cell lines resulted in decreased mRNA and protein levels of NF-κB downstream anti-apoptotic target genes. Immunoprecipitation results showed that TRIM24 could specifically bind with p65, a member of the NF-κB family. These results suggest TRIM24 may promote the proliferation and survival of CRC cells by regulating NF-κB through binding with p65. In order to confirm this hypothesis, a variety of approaches of molecular biology and cell biology will be used to explore the mechanism that TRIM24 regulates NF-κB, and verify the hypothesis in CRC mouse model, CRC organoid and tumor tissues of CRC patients. This study aims to reveal the mechanism of TRIM24 promoting the development of CRC and provide a new therapeutic target for clinical treatment.