关键词: Colon adenocarcinoma Prognosis RUNX1 Transcription factors USP31

Mesh : Humans Core Binding Factor Alpha 2 Subunit / metabolism genetics Cdc20 Proteins / metabolism genetics Ubiquitination Gene Expression Regulation, Neoplastic Minichromosome Maintenance Complex Component 2 / metabolism genetics Cell Line, Tumor Colonic Neoplasms / genetics metabolism pathology Cell Proliferation / genetics Ubiquitin-Specific Proteases / metabolism genetics Disease Progression Cell Movement / genetics

来  源:   DOI:10.1038/s41598-024-64726-w   PDF(Pubmed)

Abstract:
Colon adenocarcinoma (COAD) is the second leading cause of cancer death, and there is still a lack of diagnostic biomarkers and therapeutic targets. In this study, bioinformatics analysis of the TCGA database was used to obtain RUNX1, a gene with prognostic value in COAD. RUNX1 plays an important role in many malignancies, and its molecular regulatory mechanisms in COAD remain to be fully understood. To explore the physiological role of RUNX1, we performed functional analyses, such as CCK-8, colony formation and migration assays. In addition, we investigated the underlying mechanisms using transcriptome sequencing and chromatin immunoprecipitation assays. RUNX1 is highly expressed in COAD patients and significantly correlates with survival. Silencing of RUNX1 significantly slowed down the proliferation and migratory capacity of COAD cells. Furthermore, we demonstrate that CDC20 and MCM2 may be target genes of RUNX1, and that RUNX1 may be physically linked to the deubiquitinating enzyme USP31, which mediates the upregulation of RUNX1 protein to promote transcriptional function. Our results may provide new insights into the mechanism of action of RUNX1 in COAD and reveal potential therapeutic targets for this disease.
摘要:
结肠腺癌(COAD)是导致癌症死亡的第二大原因,仍然缺乏诊断生物标志物和治疗靶点。在这项研究中,使用TCGA数据库的生物信息学分析来获得RUNX1,这是一个在COAD中具有预后价值的基因。RUNX1在许多恶性肿瘤中起重要作用,及其在COAD中的分子调控机制仍有待充分理解。为了探索RUNX1的生理作用,我们进行了功能分析,如CCK-8,集落形成和迁移测定。此外,我们使用转录组测序和染色质免疫沉淀分析研究了潜在的机制.RUNX1在COAD患者中高表达,与生存率显著相关。沉默RUNX1显著减慢了COAD细胞的增殖和迁移能力。此外,我们证明CDC20和MCM2可能是RUNX1的靶基因,并且RUNX1可能与去泛素化酶USP31物理连接,后者介导RUNX1蛋白的上调以促进转录功能.我们的结果可能为RUNX1在COAD中的作用机制提供新的见解,并揭示该疾病的潜在治疗靶标。
公众号