Cardiomyocyte-enriched noncoding RNA (Caren) (Caren)

Cardiomyocyte-enriched noncoding RNA (Caren) is a long non-coding RNA (lncRNA) that plays a vital role in protecting the heart from failure (Nature Communications, 2021). It is highly expressed in cardiomyocytes, but its levels are markedly decreased during the progression of cardiac hypertrophy and heart failure in both mice and humans (PubMed, PMID: 33568662). Caren functions primarily by inhibiting the Ataxia-telangiectasia mutated (ATM) kinase, a key initiator of the DNA damage response. By suppressing the ATM-p53 signaling axis, Caren prevents cardiomyocyte apoptosis and maintains mitochondrial integrity and biogenesis. Research indicates that Caren also interacts with proteins involved in cardiac metabolism to ensure efficient energy production. In preclinical mouse models, the restoration of Caren levels using adeno-associated virus (AAV9) vectors has been shown to significantly improve cardiac function and survival. Because its downregulation is a hallmark of heart failure, Caren is considered a potential therapeutic target for RNA-based or gene therapy interventions. Its specific expression pattern in the heart may minimize the risk of systemic side effects, although targeted delivery remains a significant therapeutic challenge.

Other names

CarenGm12603Cardiomyocyte-enriched non-coding RNA

Caren functions by inhibiting the Ataxia-telangiectasia mutated (ATM) kinase signaling pathway, which prevents the activation of the DNA damage response and subsequent p53-mediated apoptosis in cardiomyocytes. It also promotes mitochondrial biogenesis and maintains cardiac energy metabolism by regulating heart-specific intermediate metabolism enzymes.