对比RNA-Seq分析揭示了PDX模型生成期间组织特定的剪接变异
Eun Ji Lee1, Seung-Jae Noh2, Huiseon Choi2
1Department of Physiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
International journal of molecular sciences
|December 9, 2023
概括
患者衍生异种移植 (PDX) 显示保存的RNA生物型,但改变了拼接模式,特别是跳过的前子. 胃癌PDX模型显示逆基因相关性,影响瘤完整性.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 组织特异性基因表达决定了器官功能和瘤特征.
- 了解患者衍生异体移植 (PDX) 中组织特异性如何保持对于癌症研究至关重要.
- 免疫功能受损的小鼠模型被广泛用于临床前癌症研究.
研究的目的:
- 为了比较原发性瘤及其相应的患者衍生异体移植 (PDX) 之间的基因表达和拼接模式.
- 在PDX模型中评估组织特异性基因表达的保存.
- 在PDX瘤的形成过程中识别RNA剪接的变化.
主要方法:
- 对四对原发性-PDX瘤对进行RNA测序 (RNA-seq) 的比较分析.
- 对RNA生物型分布和拼接模式的分析.
- 组织特定基因的相关性分析.
- 拼接变种特定的RT-PCR验证.
主要成果:
- 在初级瘤和PDX之间观察到保守的RNA生物型分布.
- 在PDX瘤中检测到拼接模式的显著变化,主要是跳过的外.
- 在初级和PDX对之间发现了组织特异性基因表达的强烈正相关性,胃癌除外.
- 胃癌PDX模型显示组织特异性基因表达的反相关性.
结论:
- PDX形成可以导致剪接事件的组织特异性变化.
- 拼接变化代表了影响初级-PDX关系完整性的可变因素.
- 这些发现强调了在解释PDX模型数据时考虑拼接变化的重要性.
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