Exploiting the hypoxia sensitive non-coding genome for organ-specific physiologic reprogramming

• Published in: Biochimica et biophysica acta Vol. 1863; no. 7; pp. 1782 - 1790
• Main Authors: Bischof, Corinne, Krishnan, Jaya
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-07-2016
• Subjects: Animals; Cardiomyopathies - genetics; Cardiomyopathies - metabolism; Cardiomyopathies - physiopathology; Cardiomyopathies - therapy; Cardiomyopathy; Cell Differentiation; Cell Hypoxia; Cell Proliferation; Cellular Microenvironment; Cellular Reprogramming; Cellular Reprogramming Techniques; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Therapy; Genome, Human; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - therapeutic use; Myocardium - metabolism; Myocardium - pathology; Non-coding RNA; Phenotype; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Long Noncoding - therapeutic use; Signal Transduction; Cardiomyopathy; Hypoxia; Non-coding RNA
• ISSN: 0167-4889; 0006-3002; 1879-2596
• DOI: 10.1016/j.bbamcr.2016.01.024

In this review we highlight the role of non-coding RNAs in the development and progression of cardiac pathology and explore the possibility of disease-associated RNAs serving as targets for cardiac-directed therapeutics. Contextually, we focus on the role of stress-induced hypoxia as a driver of disease development and progression through activation of hypoxia inducible factor 1α (HIF1α) and explore mechanisms underlying HIFα function as an enforcer of cardiac pathology through direct transcriptional coupling with the non-coding transcriptome. In the interest of clarity, we will confine our analysis to cardiac pathology and focus on three defining features of the diseased state, namely metabolic, growth and functional reprogramming. It is the aim of this review to explore possible mechanisms through which HIF1α regulation of the non-coding transcriptome connects to spatiotemporal control of gene expression to drive establishment of the diseased state, and to propose strategies for the exploitation of these unique RNAs as targets for clinical therapy. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.
•Non-coding RNA (ncRNA) expression is altered in heart disease.•ncRNAs play a key role in the development and progression of the disease.•Hif1α is induced in the diseased state and modulates expression of a ncRNA subset.•Disease-associated ncRNAs can be exploited for tissue-specific targeting.