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在甲状腺细胞的蛋白质水平上,其在甲状腺素-3中的多态性Pro64His具有功能后果.

Roberto Silvestri1, Lorenzo Zallocco2, Alda Corrado1

  • 1Department of Biology, Genetic Unit, University of Pisa, Pisa, Italy.

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概括

加勒-3 (加尔-3) 中的rs4644单核酸多态 (SNP) 影响蛋白质结构和表达,影响癌症风险. 这种SNP影响了gal-3

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这就是CRISPR/Cas9的作用.分化甲状腺癌 (DTC)功能多态性 rs464444 的功能多态性盖莱克-3 (gal3) 是一种蛋白质.乳头状甲状腺癌 (PTC)蛋白质组是一种蛋白质组.

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科学领域:

  • 分子生物学分子生物学
  • 遗传学 是一个遗传学.
  • 生物化学 生物化学

背景情况:

  • 加勒-3 (加尔-3) 基因 (LGALS3) rs4644单核酸多态 (SNP) 影响了加尔-3 蛋白的功能.
  • 这种SNP与分化甲状腺癌 (DTC) 和其他癌症的风险增加有关.
  • 了解RS4644SNP的生物影响对于疾病风险评估至关重要.

研究的目的:

  • 研究rs4644 SNP对gal-3蛋白结构和表达的功能影响.
  • 分析rs4644 SNP在甲状腺细胞中诱导的蛋白质和转录基因变化.
  • 阐明 rs4644 影响 gal-3 在细胞过程中的作用的机制.

主要方法:

  • 利用CRISPR-Cas9创建异构的Nthy-Ori细胞系 (NC-P64和NA-H64),仅在rs4644基因型上有所不同.
  • 进行了全面的蛋白质组分析,以确定细胞系之间差异表达的蛋白质.
  • 整合蛋白质组数据与转录组分析,以将蛋白质表达与mRNA水平相关联.

主要成果:

  • 证实了H64 (单体,同极体,异极体) 与P64 (单体,未分离的同极体) 变体的不同gal-3二元化模式.
  • 确定了显著的蛋白质表达变化,主要在NA-H64细胞上调,与rs4644.4相关.
  • 观察到rs4644影响mRNA表达和转录后调节,影响gal-3的共同调节功能.

结论:

  • rs4644 SNP通过改变二分化和基因表达调节来调节gal-3功能.
  • 这些依赖于rs4644的机制有助于不同的疾病易感性.
  • 这些发现支持gal-3基因变异在疾病风险分层中的作用.