CVD-associated non-coding RNA, ANRIL, modulates pathways in VSMC

被引：121

作者：

Congrains, Ada ^{[1
]}

Kamide, Kei ^{[1
]}

Katsuya, Tomohiro

Yasuda, Osamu ^{[2
]}

Oguro, Ryousuke ^{[1
]}

Yamamoto, Koichi ^{[1
]}

Ohishi, Mitsuru ^{[1
]}

Rakugi, Hiromi ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Suita, Osaka 5650871, Japan

[2] Kumamoto Univ Hosp, Dept Cardiovasc Clin & Translat Res, Kumamoto, Japan

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2012年 / 419卷 / 04期

关键词：

ANRIL; CDKN2BAS; 9p21; Locus; Atherosclerosis; VSMC; GENOME-WIDE ASSOCIATION; CHROMOSOME; 9P21.3; GENETIC-VARIANTS; GROWTH; LOCUS; EGF; SUSCEPTIBILITY; APOPTOSIS; MELANOMA; DISEASE;

D O I：

10.1016/j.bbrc.2012.02.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of this non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：612 / 616

页数：5

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