Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease.
Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease.
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DOI：
10.1007/82_2015_455
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发表时间：
2016
影响因子：
--
通讯作者：
Walsh MJ
中科院分区：
文献类型：
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作者：
Aguilo F;Di Cecilia S;Walsh MJ
长链非编码RNA CDKN 2B-AS 1，通常称为INK 4基因座中的反义非编码RNA（ANRIL），是从人类9号染色体p21.3上的短臂转录的3.8 kb长的RNA，其与包含与INK 4 b-ARF-INK 4a基因簇和甲基硫代腺苷磷酸化酶（MTAP）基因并列的三个主要肿瘤抑制基因座的关键区域重叠。全基因组关联研究已经确定该区域具有显著且不断增加的疾病相关DNA改变和单核苷酸多态性，这对应于对人类疾病的易感性增加。最近的注意力集中在ANRIL序列中的这些改变是否影响其表达水平和/或其剪接转录物变异，以及因此影响整体细胞内稳态。此外，最近的证据假设，ANRIL不仅可以调节他们的直接基因组邻居在顺式，但也有能力调节其他位点的反式。这种行动将进一步增加复杂性的机制，通过ANRIL和进一步的范围内，这种lncRNA在疾病的发病机制。在这一章中，我们总结了ANRIL的研究的最新发现，并提供了一个角度的生物学和临床意义的ANRIL作为一个假定的生物标志物，特别是，其潜在的作用，指导细胞的命运，导致癌症和心血管疾病。
The long non-coding RNA CDKN2B-AS1, commonly referred to as the Antisense Non-coding RNA in the INK4 Locus (ANRIL), is a 3.8-kb-long RNA transcribed from the short arm of human chromosome 9 on p21.3 that overlaps a critical region encompassing three major tumor suppressor loci juxtaposed to the INK4b-ARF-INK4a gene cluster and the methyl-thioadenosine phosphorylase (MTAP) gene. Genome-wide association studies have identified this region with a remarkable and growing number of disease-associated DNA alterations and single nucleotide polymorphisms, which corresponds to increased susceptibility to human disease. Recent attention has been devoted on whether these alterations in the ANRIL sequence affect its expression levels and/or its splicing transcript variation, and in consequence, global cellular homeostasis. Moreover, recent evidence postulates that ANRIL not only can regulate their immediate genomic neighbors in cis, but also has the capacity to regulate additional loci in trans. This action would further increase the complexity for mechanisms imposed through ANRIL and furthering the scope of this lncRNA in disease pathogenesis. In this chapter, we summarize the most recent findings on the investigation of ANRIL and provide a perspective on the biological and clinical significance of ANRIL as a putative biomarker, specifically, its potential role in directing cellular fates leading to cancer and cardiovascular disease.