在SMAD7位点上识别和描述结直肠癌相关的SNP
Zhao Liu1, Yihan Zhao1, Hongli Song1
1Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Journal of cancer research and clinical oncology
|September 18, 2023
概括
这项研究确定了SMAD7中的特定基因变异 (rs8085824) 如何影响结直肠癌 (CRC) 风险. 它表明,HNRNPK蛋白与这种变体结合会影响SMAD7表达和CRC细胞生长.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 全基因组关联研究 (GWAS) 将SMAD7基因与结直肠癌 (CRC) 易感性联系起来.
- 通过SMAD7影响CRC风险的精确分子机制在很大程度上仍未被描述.
研究的目的:
- 在SMAD7位点上识别与结直肠癌相关的功能单核酸多态 (fSNP).
- 阐明这些fSNP影响SMAD7表达和CRC发育的调节蛋白和分子机制.
主要方法:
- 使用Reel-seq. 在SMAD7位点上选功能性SNP (fSNP).
- 验证fSNP和蛋白质结合使用光酶记者测试,电泳运动转移测试 (EMSA) 和西部斑点 (WB).
- RNA干扰 (RNAi) 来敲除异质核核核糖核蛋白K (HNRNPK),并评估其对SMAD7表达和结直肠癌细胞功能的影响.
主要成果:
- 在SMAD7的链接不平衡 (LD) 中确定了8个fSNP,包括rs8085824.
- 确定了调节蛋白 (HNRNPK,H1-3,THOC6,DDX21) 与已识别的fsnps的等位基因特定结合得到证实.
- 通过降低SMAD7的调节,对HNRNPK的抑制显著抑制了结直肠癌细胞的增殖和克隆细胞的形成,SMAD7的过度表达恢复了这些功能.
结论:
- 这项研究揭示了SMAD7 fSNP rs8085824在结直肠癌易感性的功能机制.
- 结合rs8085824的HNRNPK调节SMAD7的表达,影响结直肠癌细胞的行为.
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