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在角质细胞癌中,MCPIP1调节了miRNA‒mRNA景观
Agata Lichawska-Cieslar1, Weronika Szukala1,2, Guillem Ylla3
1Faculty of Biochemistry, Biophysics and Biotechnology, Department of General Biochemistry, Jagiellonian University, Gronostajowa 7, Krakow, 30-387, Poland.
Journal of experimental & clinical cancer research : CR
|October 20, 2024
概括
丢失的MCPIP1 (单细胞化学反应蛋白1-诱导蛋白1) 改变miRNA的表达,影响皮肤癌的发展. 这项研究揭示了关键的miRNA-mRNA网络,这些网络与癌症发生过程中的炎症和扩散有关.
科学领域:
- 分子生物学分子生物学
- 在瘤学瘤学.
- 皮肤病学 皮肤病学
背景情况:
- 单细胞化疗蛋白1-诱导蛋白1 (MCPIP1/Regnase-1) 是一种消极的炎症调节剂,具有抑制瘤的功能.
- 缺乏MCPIP1在角质细胞 (Mcpip1eKO) 的小鼠对化学诱导的皮肤乳头瘤的敏感性增加.
研究的目的:
- 在皮肤状细胞癌 (SCC) 类乳头瘤中研究由MCPIP1的RNase活性控制的微RNA (miRNA) -mRNA调控网络.
- 在化学致癌过程中识别基因和miRNA表达特征的MCPIP1依赖性变化.
主要方法:
- 用RNA测序 (RNA-Seq) 和生物信息分析来识别Mcpip1eKO乳头瘤中差异表达的基因和miRNA.
- 定量PCR验证了人类角质细胞中的miRNA表达与MCPIP1沉默.
- 功能性测试和生物信息工具 (DIANA-microT-CDS,DIANA-TarBase v7) 预测和验证了miRNA目标和途径.
主要成果:
- RNA-Seq揭示了Mcpip1eKO乳头瘤中2400个差异表达的蛋白质编码基因和33个差异表达的miRNA.
- 证实MCPIP1活性调节小鼠和人类角质细胞中的miR-223-3p,miR-376c-3p和miR-139-5p表达,MCPIP1直接分裂miR-376c-3p前体.
- 这些miRNAs促进SCC样角质细胞的增殖,而MCPIP1依赖的miRNA-mRNA网络调节炎症,上皮增殖,Wnt信号和miRNA转录.
结论:
- 失去MCPIP1显著改变皮肤乳头瘤中的miRNA表达特征,影响miRNA-mRNA调节网络.
- 这些miRNA-mRNA网络的变化在调节皮肤致癌的关键途径方面发挥着至关重要的作用.
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