NURF复合体亚基BPTF靶向调节肿瘤干细胞特征因子表达在维护结直肠癌TICs干性的作用机制研究

具有肿瘤干细胞（CSCs）特征的肿瘤起始细胞（TICs）是结直肠癌（CRC）转移和治疗抗性的关键；表观遗传学调节是维持TICs干细胞的重要机制。前期研究发现circRNA募集BPTF与c-Myc基因结合，促进c-Myc表达。BPTF/NURF通过结合到基因的转录调节区域，对CSCs特征性转录因子的表达调节在TICs的CSCs特征维护中可能发挥关键作用，非编码RNA与BPTF的结合可能影响BPTF在特征性基因转录调节区域的募集。本课题假设：“BPTF参与调节其他TICs干性特征转录因子的基因表达，并通过与不同非编码RNA的结合达到靶向基因调节作用”，分析BPTF与结直肠癌TICs中CSCs相关转录调节因子的结合，BPTF对转录因子基因表达的调控作用；筛查与BPTF结合的非编码RNA成分，阐明靶向核小体重塑机制参与CRC中TICs维护机制，为了解CRC进展机制，改善临床诊疗具有重要意义。

umor initiating cells (TICs) with the characteristics of tumor stem cells (CSCs) are the key to colorectal cancer (CRC) metastasis and treatment resistance。 Epigenetic regulation is an important mechanism to maintain the stemness of TICs. Our previous research found that circRNA recruited the binging of BPTF to c-Myc gene therefore promote c-Myc expression and stemness of the cell. BPTF is the core subunit of the nuclear small remodeling factor complex NURF. BPTF / NURF can participate in the regulation of gene expression by binding to the transcriptional regulatory region of genes, in combination with non-coding RNA. BPTF/NURF binding may affect the transcriptional regulation of characteristic genes of stem cell-specific transcription factors, therefore plays a key role in the maintenance of CSCs characteristics of TICs. We hypothesize that "BPTF participates in the regulation of gene expression of other TICs' characteristic transcription factors of stem cells by combining with different non-coding RNAs." In this topic, we will analyze the binding of BPTF to CSCs-related transcriptional regulator genes in colorectal cancer TICs; the effect of BPTF expression changes on the gene expression of these transcription factors; and screen non-coding RNA components that bind to BPTF. The results will help to clarify the mechanism that BPTF/NURF is involved in the maintenance of TICs in CRC. The results of this topic are of great significance for further understanding the mechanism of CRC disease progression and improving clinical diagnosis and treatment.