A long noncoding RNA CHAIR protects the heart from pathological stress.

Mammalian genomes have been found to be extensively transcribed. In addition to classic protein coding genes, a large numbers of long noncoding genes (lncRNAs) have been identified, while their functions, especially in heart diseases, remain to be established. We hypothesized that heart failure progression is controlled by tissue-specific lncRNAs. In the present study, we found that the cardiac-enriched lncRNA 4632428C04Rik, named as cardiomyocyte hypertrophic associated inhibitory RNA (CHAIR), is dynamically regulated during heart development, is expressed at low levels in embryonic hearts and accumulated at high levels in adult hearts. More interestingly, the lncRNA was down-regulated during cardiac hypertrophy and failure both in mice and humans. Importantly, loss of lncRNA CHAIR has no effects on normal hearts, whereas it results in accelerated heart function decline, increased hypertrophy, and exacerbated heart failure in response to stress. In contrast, restoring the expression of lncRNA CHAIR rescued the hearts from hypertrophy and failure. DNMT3A was recruited to CHAIR promoter during heart failure to suppress its expression. Reciprocally, CHAIR interacted with DNMT3A to inhibit its DNA-binding activity. Taken together, our data revealed a new cardioprotective lncRNA that represses heart failure through an epigenetic mechanism.

Qian Y ，Zhang M ，Zhou N ，Xu X ，Zhang J ，Ding Q ，Wang J ... -  《-》

Long Noncoding RNA Ahit Protects Against Cardiac Hypertrophy Through SUZ12 (Suppressor of Zeste 12 Protein Homolog)-Mediated Downregulation of MEF2A (Myocyte Enhancer Factor 2A).

Yu J ，Yang Y ，Xu Z ，Lan C ，Chen C ，Li C ，Chen Z ，Yu C ，Xia X ，Liao Q ，Jose PA ，Zeng C ，Wu G ... -  《-》

The H19 long noncoding RNA is a novel negative regulator of cardiomyocyte hypertrophy.

The H19 lncRNA, a highly abundant and conserved imprinted gene, has been implicated in many essential biological processes and diseases. However, the function of H19 in the heart remains unknown. In this study, we investigated the function and underlying mechanism of H19 in regulating cardiomyocyte hypertrophy. We first detected the expression of H19 and its encoded miR-675 in both normal and diseased hearts and verified their up-regulations in pathological cardiac hypertrophy and heart failure. Adenovirus-mediated expression and a siRNA-mediated silence of H19 showed that H19 overexpression reduced cell size both at baseline and in response to phenylephrine, whereas knock-down of H19 induced cardiomyocyte hypertrophy. Overexpression or knock-down of miR-675 in cardiomyocytes demonstrated that miR-675 also inhibited cardiomyocyte hypertrophy. Moreover, inhibition of miR-675 reversed the reduction of cardiomyocyte size in H19-overexpressing cardiomyocytes, while infection with an adenovirus carrying H19 fragment without pre-miR-675 (H19-Tru) or with mutant sequences of pre-miR-675 (H19-Mut) failed to reduce cardiomyocyte size, indicating that miR-675 mediated the inhibitory effect of H19 on cardiomyocyte hypertrophy. We also identified that CaMKIIδ was a direct target of miR-675 and partially mediated the effect of H19 on cardiomyocyte hypertrophy. Furthermore, in vivo silencing of miR-675 using a specific antagomir in a pressure overload-induced mouse model of heart failure increased cardiac CaMKIIδ expression and exacerbated cardiac hypertrophy. These findings reveal a novel function of H19-miR-675 axis targeting CaMKIIδ as a negative regulator of cardiac hypertrophy, suggesting its potential therapeutic role in cardiac diseases.

Liu L ，An X ，Li Z ，Song Y ，Li L ，Zuo S ，Liu N ，Yang G ，Wang H ，Cheng X ，Zhang Y ，Yang X ，Wang J ... -  《-》

Long Noncoding RNA CPR (Cardiomyocyte Proliferation Regulator) Regulates Cardiomyocyte Proliferation and Cardiac Repair.

Ponnusamy M ，Liu F ，Zhang YH ，Li RB ，Zhai M ，Liu F ，Zhou LY ，Liu CY ，Yan KW ，Dong YH ，Wang M ，Qian LL ，Shan C ，Xu S ，Wang Q ，Zhang YH ，Li PF ，Zhang J ，Wang K ... -  《-》

A long noncoding RNA protects the heart from pathological hypertrophy.

Han P ，Li W ，Lin CH ，Yang J ，Shang C ，Nuernberg ST ，Jin KK ，Xu W ，Lin CY ，Lin CJ ，Xiong Y ，Chien H ，Zhou B ，Ashley E ，Bernstein D ，Chen PS ，Chen HV ，Quertermous T ，Chang CP ... -  《-》