Long noncoding RNAs in cardiovascular disease, diagnosis, and therapy

Abstract

Purpose of review Long non-coding RNAs (lncRNAs) have emerged as powerful regulators of nearly all biological processes. Their cell-type and tissue-specific expression in health and disease provides new avenues for diagnosis and therapy. This review highlights the role of lncRNAs that are involved in cardiovascular disease (CVD) with a special focus on cell types involved in cardiac injury and remodelling, vascular injury, angiogenesis, inflammation, and lipid metabolism. Recent findings Almost 98% of the genome does not encode for proteins. LncRNAs are among the most abundant type of RNA in the non-coding genome. Accumulating studies have uncovered novel lncRNA-mediated regulation of CVD-associated genes, signalling pathways, and pathophysiological responses. Targeting lncRNAs in vivo using short antisense oligonucleotides or by gene editing has provided important insights into disease pathogenesis through epigenetic, transcriptional, or translational mechanisms. Although cross-species conservation still remains a major obstacle, there is increasing appreciation that altered expression of lncRNAs associates with stage-specific CVD pathologies and in human patient cohorts, providing new opportunities for diagnosis and therapy. Summary A better understanding of lncRNAs will not only fundamentally improve our understanding of key signaling pathways in CVD, but also aid in the development of effective new therapies and RNA-based biomarkers.

Silencing of MEG3 inhibited ox‐LDL‐induced inflammation and apoptosis in macrophages via modulation of the MEG3/miR‐204/CDKN2A regulatory axis

“…In recent decades, long noncoding RNAs (lncRNAs), a new class of evolutionarily conserved RNAs with lengths longer than 200 nucleotides and lacking protein coding capability, have been widely identified and researched (Mattick and Rinn, 2015). LncRNAs affect the physiological and pathological progression of a variety of human diseases, including diabetic nephropathy, autoimmune diseases, immune-related diseases, neurodegenerative diseases, human cancers, metabolic diseases, and cardiovascular-related diseases (Adams et al, 2017;Chen et al, 2017;Haemmig et al, 2017;Rogoyski et al, 2017). LncRNAs affect the physiological and pathological progression of a variety of human diseases, including diabetic nephropathy, autoimmune diseases, immune-related diseases, neurodegenerative diseases, human cancers, metabolic diseases, and cardiovascular-related diseases (Adams et al, 2017;Chen et al, 2017;Haemmig et al, 2017;Rogoyski et al, 2017).…”

“…Despite their original definition of "transcriptional noise," lncRNAs play roles multiple biological processes, including chromatin dynamics, cell growth, cell proliferation, cell apoptosis, cell differentiation, cell metastasis, the cell cycle and tumorigenesis via the modulation of gene expression at the transcriptional, posttranscriptional and translational levels (Quinn and Chang, 2016;Sun et al, 2017). LncRNAs affect the physiological and pathological progression of a variety of human diseases, including diabetic nephropathy, autoimmune diseases, immune-related diseases, neurodegenerative diseases, human cancers, metabolic diseases, and cardiovascular-related diseases (Adams et al, 2017;Chen et al, 2017;Haemmig et al, 2017;Rogoyski et al, 2017). Recent research has demonstrated that several lncRNAs, including UCA1, MALAT1, TUG1, NEAT1, HOTAIR, DIGIT, H19, and MEG3, play important roles in AS (Liu et al, 2017a, b;Sallam et al, 2018;Yu and Wang, 2018).…”

Long Non-Coding RNAs in Vascular Inflammation

“…Other considerations include whether the lncRNA acts in cis or trans and whether the RNA product itself is essential for fulfilling its function or if its transcription per se that underlies its function ( 12 ). However, the role of lncRNAs in vascular inflammation and CVD is just emerging ( 13 ). This review will summarize recent findings that provide mechanistic and translational insights of lncRNAs in acute and chronic vascular inflammation in the context of CVD.…”

miR‐185 affected the EMT, cell viability, and proliferation via DNMT1/MEG3 pathway in TGF‐β1‐induced renal fibrosis

“…Although previously known as "transcriptional noise," lncRNAs are proved to participate in a variety of cellular processes, including cell growth, cell proliferation, cell differentiation, cell migration, cycle, embryonic development, and tumorigenesis through regulating gene expression at both transcriptional and post-transcriptional levels (Mercer et al, 2009;Guttman and Rinn, 2012;Rogoyski et al, 2017). In recent decades, researches documented that lncRNAs were involved in variety of human diseases, such as respiratory system-related diseases, immune system-related diseases, nervous systemrelated diseases, endocrine related diseases, cardiovascular disease, urogenital system-related diseases, and variety of cancers (Wapinski and Chang, 2011;Batista and Chang, 2013;Latronico and Condorelli, 2015;Haemmig et al, 2017;Rogoyski et al, 2017). Reports demonstrated that several lncRNAs were involved in the TGF-β-induced renal fibrosis, including lncRNA H19, lncRNA ENSMUST00000147869, lincRNA-Gm4419, lncRNA Erbb4-IR, and so on (Jiang and Zhang, 2017;Sun et al, 2017).…”