The Present and Future
State-of-the-Art Review
Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets?

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Abstract

Recent studies suggest that the majority of the human genome is transcribed, but only about 2% accounts for protein-coding exons. Long noncoding RNAs (lncRNAs) constitute a heterogenic class of RNAs that includes, for example, intergenic lncRNAs, antisense transcripts, and enhancer RNAs. Moreover, alternative splicing can lead to the formation of circular RNAs. In support of putative functions, GWAS for cardiovascular diseases have shown predictive single-nucleotide polymorphisms in lncRNAs, such as the 9p21 susceptibility locus that encodes the lncRNA antisense noncoding RNA in the INK4 locus (ANRIL). Many lncRNAs are regulated during disease. For example, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and myocardial infarction-associated transcript (MIAT) were shown to affect endothelial cell functions and diabetic retinopathy, whereas lincRNA-p21 controls neointima formation. In the heart, several lncRNAs were shown to act as microRNA sponges and to control ischemia-reperfusion injury or act as epigenetic regulators. In this review, the authors summarize the current understanding of lncRNA functions and their role as biomarkers in cardiovascular diseases.

Key Words

cardiac
long noncoding RNA
microRNA
vascular

Abbreviations and Acronyms

ANRIL
antisense noncoding RNA in the INK4 locus
APF
autophagy-promoting factor
Bvht
Braveheart
CAD
coronary artery disease
CARL
cardiac-apoptosis related long noncoding RNA
Cas9
CRISPR-associated protein 9
CDKN2B
cyclin-dependent kinase inhibitor 2B
CHRF
cardiac hypertrophy related factor
circRNA
circular RNA
CRISPR
clustered regularly interspaced short palindromic repeats
GWAS
genome-wide association studies
lncRNA
long noncoding RNA
MALAT1
metastasis-associated lung adenocarcinoma transcript 1
MDRL
mitochondrial dynamic related long noncoding RNA
Mhrt
myosin heavy chain-associated RNA transcript
MIAT
myocardial RNA transcript
miRNA
micro–RNA
mRNA
messenger RNA
NFIA
nuclear factor IA
PRC1
polycomb repressive complex 1
PRC2
polycomb repressive complex 2
SENCR
smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA
shRNA
small hairpin RNA
siRNA
small interfering RNA
SNP
single-nucleotide polymorphism

Cited by (0)

Drs. Boon, Jaé, and Dimmeler have filed for a patent regarding long noncoding RNAs in cardiovascular disease. Dr. Holdt has reported that she has no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.