长非编码RNAMALAT1通过特定癌细胞类型的下游调节元件调节NR4A1表达
Sara Wernig-Zorc1,2, Uwe Schwartz3, Paulina Martínez-Rodríguez4
1Regensburg Center for Biochemistry [RCB], Universität Regensburg, 93053 Regensburg, Germany.
International journal of molecular sciences
|May 25, 2024
概括
转移相关的肺腺癌转录1 (MALAT1) 通过改变调控元素的可访问性来微调NR4A1基因表达. 这种机制是特定于细胞类型的,在乳腺癌中观察到,但不是胰腺癌.
科学领域:
- 分子生物学分子生物学
- 基因组学就是基因组学.
- 癌症研究 癌症研究
背景情况:
- 长非编码RNAs (lncRNAs) 调节基因表达,并与癌症有关.
- 关于lncRNA对基因调节元件 (RE) 的影响的了解有限.
研究的目的:
- 研究MALAT1 lncRNA如何通过调控元素影响基因表达.
- 为了阐明MALAT1/NR4A1监管轴.
主要方法:
- 时间解决的MALAT1敲击,随后是并行RNA-seq和ATAC-seq.
- 克里斯普尔干扰 (克里斯普尔-i) 测试.
- 对癌症基因组图谱 (TCGA) 数据的分析.
- 在乳腺和胰腺癌细胞系中进行实验验证.
主要成果:
- 马拉特1突击降低了NR4A1基因下游的可访问性,与NR4A1表达减少相关.
- 确定了一个功能MALAT1/NR4A1轴,涉及NR4A1下游RE.
- 在乳腺癌中发现NR4A1表达和RE可访问性之间的正相关性,但胰腺癌没有.
结论:
- MALAT1通过调节下游RE的可访问性来微调NR4A1表达式.
- 这种调节机制是细胞类型特定的,在乳腺癌细胞 (MCF7) 中得到验证,但不是胰腺癌细胞 (PANC1).
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