Table 3 |.
lncRNAs involved in cardiomyocyte proliferation, cardiac regeneration or cardiac conduction
| lncRNA | Models | Functions | Interactions and effects | Ref. |
|---|---|---|---|---|
| AZIN2-sv (AZIN2-splice variant)172,173 | Rat | AZIN2-sv suppresses endogenous cardiac regeneration by targeting the PTEN-AKT pathway; knock-down of AZIN2-sv attenuates ventricular remodelling and improves cardiac function after myocardial infarction | Stabilizes PTEN through binding; acts as a sponge of miRNA-214 to release PTEN | 172 |
| APF (autophagy promoting factor) | Mouse | Inhibition of APF reduces ischaemia-reperfusion injury after myocardial infarction in vivo | Binds to and regulates miRNA-188–3p | 174 |
| CAIF (cardiac autophagy inhibitory factor) | In vitro (cardiomyocytes) | CAIF suppresses cardiac autophagy and attenuates damage from myocardial infarction | Binds to p53 protein and blocks p53-mediated myocardin transcription | 175 |
| CARMEN (cardiac mesoderm enhancer-associated non-coding RNA) | Human and mouse | Expression of CARMEN is activated during pathological remodelling in mouse and human hearts; necessary for maintaining cardiac identity in differentiated cardiomyocytes; knock-down inhibits specification and differentiation in cardiac precursor cells | Interacts with SUZ12 and EZH2 | 176 |
| CCRR (cardiac conduction regulatory RNA; AK045950) | Human and mouse | CCRR is downregulated in humans with heart failure and a mouse model of heart failure; inhibition of CCRR induces arrhythmias in healthy mice (eliminated by CCRR overexpression); heart failure or CCRR knock-down damages intercalated discs and gap junctions to slow longitudinal cardiac conduction | Binds to CIP85 | 48 |
| CRRL (cardiomyocyte regeneration-related lncRNA) | Mouse | Loss of CRRL attenuates remodelling after myocardial infarction and preserves cardiac function in adult rats; CRRL promotes cardiomyocyte proliferation | CRRL acts as a competing endogenous RNA by binding to miRNA-199a-3p, which results in increased expression of HOPX | 177 |
| ECRAR (endogenous cardiac regeneration-associated regulator) | Human and rat | Promotes DNA synthesis, mitosis and cytokinesis in postnatal day 7 and adult rat cardiomyocytes; overexpression stimulates myocardial regeneration after myocardial infarction; knock-down of ECRAR inhibited postnatal day 1 cardiomyocyte proliferation and prevented recovery after myocardial infarction | ECRAR directly binds and promotes phosphorylation of ERK1/2, resulting in activation of cyclin D1 and cyclin E1, which, in turn, activate E2F1 | 178 |
| Meg3 (maternally expressed gene 3) | Human | Meg3 was increased in samples from patients with heart failure; Meg3 has been shown to have pro-apoptotic properties; mice with Meg3 knock-down show improvement in cardiac function after myocardial infarction | Interacts with the RNA-binding protein FUS | 179 |
| Wisper (WISP2 super-enhancer-associated RNA) | Mouse | Enriched in cardiac fibroblasts; antisense oligonucleotide-mediated silencing of Wisper in vivo attenuates myocardial infarction-induced fibrosis and cardiac dysfunction | Associates with TIAL1 to control expression of a profibrotic form of PLOD2 (which is involved in collagen crosslinking and stabilization of the extracellular matrix) | 134 |
Long non-coding RNAs (lncRNAs) with roles in other cardiac growth processes and functions have also been defined. This list of lncRNAs overlaps with those that affect cardiac hypertrophy. miRNA, microRNA.