长非编码RNAABHD11-AS1与SART3相互作用,并调节CD44RNA替代拼接以促进肺癌发生
Po-Shun Wang1, Zulong Liu1, Osama Sweef2
1Stony Brook Cancer Center, Stony Brook University, Stony Brook, NY, USA; Division of Cancer Biology, Department of Medicine, MetroHealth Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Environment international
|February 16, 2024
概括
六价 (Cr(VI)) 暴露对长非编码RNAABHD11-AS1进行上调,通过改变CD44RNA剪接来促进肺癌的发展和干性. 这一发现澄清了Cr (VI) 诱导的肺癌发生的一个关键机制.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 六价 (Cr(VI)) 是一种与人类肺癌有关的环境污染物,但其致癌机制尚不清楚.
- 肺癌仍然是癌症死亡的主要原因,人们对其发育和进展途径了解甚少.
- 长非编码RNAs (lncRNAs) 与癌症有关,但它们在致癌过程中的特定作用需要进一步阐明.
研究的目的:
- 研究 lncRNA ABHD11-AS1 在 Cr (VI) 诱导的肺癌发生中的作用.
- 阐明ABHD11-AS1有助于恶性转变和癌症干的分子机制.
主要方法:
- 在Cr (VI) 暴露细胞,小鼠肺组织和人类肺癌样本中分析ABHD11-AS1表达.
- 生物信息分析将ABHD11-AS1水平与肺腺癌 (LUAD) 患者存活率相关联.
- 研究ABHD11-AS1,SART3,USP15,PRPF19和CD44替代拼接之间的相互作用.
主要成果:
- 在Cr (VI) 暴露的细胞,组织和人类肺癌细胞,特别是LUAD中,ABHD11-AS1的表达显著上调.
- 升高的ABHD11-AS1与LUAD患者的整体存活率较差相关.
- ABHD11-AS1直接结合SART3,促进USP15的核定位,从而增强CD44的替代拼接,激活β-catenin和癌症干性.
结论:
- lncRNA ABHD11-AS1在Cr(VI) 诱导的肺癌发生和癌症干性中发挥着关键作用.
- 该ABHD11-AS1/SART3/USP15通路调节CD44的替代拼接,有助于恶性转变.
- 这些发现为环境致癌物诱导的肺癌的分子机制提供了新的见解.
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