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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
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H19 是一种PERK调节的长非编码RNA,可以微调UPR信号,并抑制内分泌网膜压力诱导的细胞死亡.

Wen Liu1, Ananya Gupta2, Michael Kerin3

  • 1Discipline of Pathology, Cancer Progression and Treatment Research Group, Lambe Institute for Translational Research, School of Medicine, University of Galway, H91TK33 Galway, Ireland.

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概括

展开的蛋白质反应 (UPR) 通过PERK通路下调H19长非编码RNA (lncRNA). H19影响UPR信号传递,影响细胞命运,高表达与乳腺癌预后不佳有关.

关键词:
H19 H19 是一种H19病毒.乳腺癌 乳腺癌 乳腺癌细胞死亡,细胞死亡.细胞内膜网膜的压力应激长非编码RNA是什么意思三重阴性乳腺癌是什么不折叠的蛋白质反应反应

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科学领域:

  • 细胞生物学 细胞生物学
  • 分子生物学分子生物学
  • 癌症研究 癌症研究

背景情况:

  • 细胞内膜网膜 (ER) 应激反应涉及展开的蛋白质反应 (UPR) 恢复平衡.
  • 长非编码RNAs (lncRNAs) 越来越多地被认为是它们在细胞过程中的作用,包括ER恒温.
  • UPR和lncRNA表达之间的相互作用是一个活跃的研究领域.

研究的目的:

  • 为了研究在ER压力期间 lncRNA H19表达的调节.
  • 为了确定介导H19下调的特定UPR通路.
  • 阐明H19在UPR信号传递中的功能作用及其对乳腺癌的影响.

主要方法:

  • 利用了PERK.的遗传 (敲除) 和药理上的抑制/激活.
  • 使用的细胞系包括MCF7,T47D,293T和MDA-MB-231.
  • 对乳腺癌患者队列进行生物信息分析.

主要成果:

  • 在ER压力下调节H19 lncRNA表达以PERK依赖的方式.
  • 过度表达的H19调节ATF6,PERK和IRE1-XBP1 UPR通道.
  • 异位H19在TNBC细胞中赋予了对ER压力诱导的亡的抵抗力.
  • 高H19表达与乳腺癌的预后不佳相关,特别是基底类型的亚型.

结论:

  • H19是一种新的UPR调节的lncRNA,主要由PERK通路控制.
  • H19在调节UPR信号传递和在ER压力下影响细胞命运方面发挥着重要作用.
  • 在某些乳腺癌亚型中,H19代表了潜在的预后生物标志物和治疗点.