Table 1 |.
lncRNAs that induce cardiac hypertrophy and/or heart failure
| lncRNA | Models | Functions | Interactions and effects | Ref. |
|---|---|---|---|---|
| ANRIL (antisense non-coding RNA in the INK4 locus) | Rat (diabetic model) | Downregulated ANRIL improved cardiac function index and decreased expression of inflammatory factors, resulting in decreased myocardial collagen deposition area and cardiomyocyte apoptosis and reduced levels of oxidative stress in myocardial tissue | Not determined | 150 |
| Chaer (cardiac-hypertrophy-associated epigenetic regulator) | Mouse | Associated with the development of cardiac hypertrophy | Interacts with the catalytic subunit of PRC2 | 82 |
| CHAIR (cardiomyocyte hypertrophic associated inhibitory RNA; 4632428C04Rik) | Human and mouse | Loss of CHAIR has no effect on normal hearts; however, in response to stress, it accelerates heart functional decline, increases hypertrophy and exacerbates heart failure | Interacts with DNMT3A to inhibit its DNA-binding activity | 151 |
| Chast (cardiac hypertrophy-associated transcript) | Human and mouse | Virus-based overexpression of Chast is sufficient to induce cardiomyocyte hypertrophy in vitro and in vivo; GapmeR-mediated silencing of Chast both prevented and attenuated TAC-induced pathological cardiac remodelling, with no toxicological signs or adverse effects | Negatively regulates PLEKHM1 (located on the opposite strand to Chast), which impedes cardiomyocyte autophagy and drives hypertrophy | 81 |
| CHRF (cardiac hypertrophy related factor)73,152 | Mouse and in vitro model | Small interfering RNA-mediated knockdown of CHRF attenuates ANF and MHCβ levels in the heart | Binds to miRNA-489 to reduce its levels (microRNA sponge) | 73 |
| Fendrr (FOXF1 adjacent non-coding developmental regulatory RNA) | Mouse and in vitro model | Fendrr loss of function reduces cardiac fibrosis induced by TAC | Binds to miRNA-106b | 153 |
| Gm15834 | Mouse (TAC and angiotensin II infusion models) | Forced expression of Gm15834 increases cardiomyocyte autophagy and promotes myocardial hypertrophy; silencing of Gm15834 attenuates autophagy-induced myocardial hypertrophy | Binds to miRNA-30b-3p to function as an endogenous sponge | 154 |
| HypERlnc (hypoxia-induced endoplasmic reticulum stress regulating long non-coding RNAs)155,156 | In vitro | Silencing of HypERlnc decreases cell viability and proliferation and results in pericyte dedifferentiation; associated with increased endothelial permeability in co-cultures consisting of human primary pericyte and human coronary microvascular endothelial cells | Endoplasmic reticulum stress-related transcription factors were prominently activated by HypERlnc knockdown | 155 |
| LncDACH1 (long non-coding RNA-Dachshund homologue 1; DACH1) | Mouse | Transgenic overexpression of LncDACH1 in cardiomyocytes leads to impaired cardiac function, reduced calcium transient and cell shortening, and decreased SERCA2a protein expression; by contrast, conditional knockout of LncDACH1 in TAC-treated mouse cardiomyocytes results in increased calcium transients, cell shortening and SERCA2a protein expression and improved cardiac function | Binds to SERCA2a | 157 |
| lncExACT1 (long non-coding exercise associated transcript 1) | Mouse (exercise model) | lncExACT1 inhibition induced physiological hypertrophy and cardiomyogenesis | Interacts with DCHS2 | 158,159 |
| MIAT (myocardial infarction-associated transcript) | Mouse (myocardial infarction model) | Inhibition of MIAT protects the heart against myocardial infarction | Interacts with miRNA-150 and HOXA4 | 99 |
| Mouse (TAC and angiotensin II infusion models) | Genetic ablation of MIAT attenuates pathological hypertrophy and heart failure | Not available | 97 | |
| Meg3 (maternally expressed gene 3)135,136 | Human (induced pluripotent stem cells) and mouse | Inhibition of Meg3 in vivo after TAC prevented cardiac MMP2 induction, leading to decreased cardiac fibrosis and improved diastolic performance; mostly expressed by cardiac fibroblasts; undergoes transcriptional downregulation during late cardiac remodelling | Interacts with p53 to increase its binding and activity, inducing expression of profibrotic MMP2 gene | 136 |
| In vitro | Silenced Meg3 inhibited cardiomyocyte hypertrophy and reversed other hypertrophic responses | Might regulate miRNA-361–5p and HDAC9 by acting as a competing endogenous RNA; upregulated by the transcription factor STAT3 | 160 | |
| NRON (non-coding repressor of nuclear factor of activated T cells) | Mouse (TAC model) | In a gain-of-function mouse model, hypertrophic cardiomyopathy is worsened; by contrast, loss of function attenuates symptoms | Influences the transcription programme for hypertrophic cardiomyopathy; nuclear localization | 161 |
| Sirt1-as (silent information regulator 1-antisense) | Mouse | Overexpression of Sirt1-as increases cardiomyocyte proliferation, attenuates cardiomyocyte apoptosis, improves cardiac function and decreases mortality after myocardial infarction | Binds to the Sirt1 3′-UTR to increase the stability of Sirtl mRNA and increase abundance at both the mRNA and protein levels | 162 |
Multiple long non-coding RNAs (lncRNAs) have been described with roles in heart development and cardiac cell growth. lncRNAs with defined roles in cardiac hypertrophy and/or heart failure are described here, but this list is rapidly expanding. Some lncRNAs are presented on two rows due to substantial differences in the experimental research design and/or conclusions. miRNA, microRNA; TAC, transverse aortic constriction; UTR, untranslated region.