Cardiovascular Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Dis Markers. 2022 Feb 9;2022:8859677. doi: 10.1155/2022/8859677. eCollection 2022.
There is a huge number of noncoding RNA (ncRNA) transcripts in the cell with important roles in modulation of different mechanisms. ANRIL is a long ncRNA with 3.8 kb length that is transcribed in the opposite direction of the INK4/ARF locus in chromosome 9p21. It was shown that polymorphisms within this locus are associated with vascular disorders, notably coronary artery disease (CAD), which is considered as a risk factor for life-threatening events like myocardial infarction and stroke. ANRIL is subjected to a variety of splicing patterns producing multiple isoforms. Linear isoforms could be further transformed into circular ones by back-splicing. ANRIL regulates genes in atherogenic network in a positive or negative manner. This regulation is implemented both locally and remotely. While CAD is known as a proliferative disorder and cell proliferation plays a crucial role in the progression of atherosclerosis, the functions of ANRIL and CAD development are intertwined remarkably. This makes ANRIL a suitable target for diagnostic, prognostic, and even therapeutic aims. In this review, we tried to present a comprehensive appraisal on different aspects of ANRIL including its location, structure, isoforms, expression, and functions. In each step, the contribution of ANRIL to atherosclerosis is discussed.
细胞中有大量的非编码 RNA(ncRNA)转录本,它们在调节不同机制方面发挥着重要作用。ANRIL 是一种长 ncRNA,长度为 3.8kb,在染色体 9p21 的 INK4/ARF 基因座的反方向转录。研究表明,该基因座内的多态性与血管疾病有关,特别是冠状动脉疾病(CAD),CAD 被认为是危及生命的事件(如心肌梗死和中风)的危险因素。ANRIL 存在多种剪接模式,可产生多种异构体。线性异构体可通过反向剪接进一步转化为环状异构体。ANRIL 以正或负的方式调节动脉粥样硬化网络中的基因。这种调节既可以在局部进行,也可以在远程进行。虽然 CAD 被认为是一种增殖性疾病,细胞增殖在动脉粥样硬化的进展中起着至关重要的作用,但 ANRIL 的功能和 CAD 的发展之间存在显著的相互交织。这使得 ANRIL 成为诊断、预后甚至治疗的理想靶点。在这篇综述中,我们试图全面评估 ANRIL 的不同方面,包括其位置、结构、异构体、表达和功能。在每一步中,都讨论了 ANRIL 对动脉粥样硬化的贡献。