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SRF和CBP共同调节头部和部状细胞癌中的整合素β6过度表达
Mingyan Xu1, Gongwei Luo2, Yixin Xiao2
1Department of Implantology, Stomatological Hospital of Xiamen Medical College & Xiamen Key Laboratory of Stomatological Disease Diagnosis and Treatment, Xiamen, Fujian, China; Department of Basic Medical Science & Department of Stomatology, School of Medicine, Xiamen University, Xiamen, Fujian, China.
血清响应因子 (SRF) 和CBP介导的基因素过乙化驱动整合素β6 (ITGB6) 在头部和部状细胞癌 (HNSCC) 的过度表达. 这种表观遗传机制促进癌症的入侵和转移,影响患者的预后.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 集成蛋白β6 (ITGB6) 过度表达是攻击性头支状细胞癌 (HNSCC) 的标志,与患者的不良结果相关.
- 在HNSCC中ITGB6上调的基础上的精确分子机制在很大程度上仍未定义.
研究的目的:
- 阐明控制ITGB6在HNSCC中的表达的转录调节和表观遗传修饰.
- 确定涉及ITGB6过度表达的关键分子参与者及其临床相关性.
主要方法:
- 在HNSCC组织微阵列上进行免疫组织化学,以评估ITGB6表达和临床相关性.
- 路西法酶记者测定,位点定向突变发生和RNA干扰以研究转录调节.
- 染色体免疫沉试验和4 - 尼托基诺林-1-氧化物 (4NQO) 诱导的HNSCC小鼠模型来研究表观遗传机制.
主要成果:
- 在HNSCC组织中ITGB6表达的升高与较差的临床预后有关.
- 转录因子血清反应因子 (SRF) 被确定为ITGB6转录的关键激活剂.
- 通过CBP介导的素H3和H4过乙化增强了SRF与ITGB6促进体的结合,导致其过度表达.
结论:
- 在HNSCC中,SRF和CBP介导的基因素过乙化是关键的表观遗传机制,负责ITGB6过度表达.
- 这些发现突显了表观遗传调节在HNSCC攻击性表型中的作用,并表明了潜在的治疗点.
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