Dataset Information

Circular RNAs in rat models of cardiovascular and renal diseases.

ABSTRACT: Circular RNAs (circRNAs) have emerged as an important new class of genomic regulatory molecules contributing to the development of various diseases, but their relevance to the development and progression of hypertension remains largely unknown. A major impediment to begin studying circRNAs in rat models of inherited hypertension is that the rat as a valuable model of human diseases lags far behind the mouse and human in providing knowledge on circRNAs. In this study, a genome-wide circRNA profiling was performed from four rat strains that are widely used in hypertension research: the Dahl salt-sensitive rat (S), the Dahl salt-resistant rat (R), the spontaneously hypertensive rat (SHR), and the Wistar Kyoto rat (WKY). Combined hybridization data obtained from these four strains allowed for the identification of 12,846 circRNAs as being expressed in the rat kidneys. Out of these, 318 and 110 circRNAs were differentially expressed with a fold change > 1.5 (P < 0.05) in S vs. R and SHR vs. WKY, respectively. Among these circRNAs, circRNA/microRNA interaction was predicted since circRNAs are known as microRNA sponges to sequester microRNAs. Several circRNAs were further validated by quantitative real-time PCR. To our knowledge, our study is the primary report of profiling circRNAs in renal tissue and illustrates that circRNAs could be candidate genetic factors controlling blood pressure.

SUBMITTER: Cheng X

PROVIDER: S-EPMC5625271 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Circular RNAs in rat models of cardiovascular and renal diseases.

Cheng Xi X Joe Bina B

Physiological genomics 20170804 9

Circular RNAs (circRNAs) have emerged as an important new class of genomic regulatory molecules contributing to the development of various diseases, but their relevance to the development and progression of hypertension remains largely unknown. A major impediment to begin studying circRNAs in rat models of inherited hypertension is that the rat as a valuable model of human diseases lags far behind the mouse and human in providing knowledge on circRNAs. In this study, a genome-wide circRNA profil ...[more]

PMID: 28778982

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Project description:Heart failure, coronary artery disease and myocardial infarction are the most prominent cardiovascular diseases contributing significantly to death worldwide. In the majority of situations, except for surgical interventions and transplantation, there are no reliable therapeutic approaches available to address these health problem. Despite several advances that led to the development of biomarkers and therapies based on the renin-angiotensin system, adrenergic pathways, etc, more definitive and consistent biomarkers and specific target based molecular therapies are still being sought. Recent advances in the field of genomic research has helped in identifying non-coding RNAs, including circular RNAs, piRNAs, micro RNAs, and long non-coding RNAs, that play a significant role in the regulation of gene expression and function and have direct impact on pathophysiological mechanisms. This new knowledge is currently being explored with much hope for the development of novel treatments and biomarkers. Circular RNAs and micro RNAs have been described in myocardium and aortic valves and were shown to be involved in the regulation of pathophysiological processes that potentially contribute to cardiovascular diseases. Approximately 32?000 human exonic circular RNAs have been catalogued and their functions are still being ascertained. In the heart, circular RNAs were shown to bind micro RNAs in a specific manner and regulate the expression of transcription factors and stress response genes, and expression of these non-coding RNAs were found to change in conditions such as cardiac hypertrophy, heart failure and cardiac remodelling, reflecting their significance as diagnostic and prognostic biomarkers. In this review, we address the present state of understanding on the biogenesis, regulation and pathophysiological roles of micro and circular RNAs in cardiovascular diseases, and on the potential future perspectives on their use as biomarkers and therapeutic agents.

Project description:Circular RNAs are characterized as a class of covalently closed circular RNA transcripts and are associated with a variety of cellular processes and neurological diseases by sponging microRNAs. Expression profiling of circular RNAs in glaucoma, which is a form of optic neuropathy, has not been performed to date. The most common characteristic of all forms of glaucoma is the loss of retinal ganglion cells. While the pathogenesis of glaucoma is not fully understood, intraocular pressure is unquestionably the only proven modifiable factor which makes chronic ocular hypertension (COH) animals the classical glaucoma models. Based on these findings, we completed the first in-depth study of rat retinal circular RNA expression profiling to identify probable biomarkers for the diagnosis of glaucoma. Two ocular hypertension models were induced by episcleral vein ligation (EVL) and microbead injection in rats. Overall, 15,819 circular RNA were detected. Furthermore, 3,502 differentially expressed circular RNAs verified in both COH rats were identified, of which 691 were upregulated and 2,811 were downregulated. Seven significantly downregulated (both log2FoldChange < -2.5 and adjusted P < 0.001) and seven significantly upregulated (both log2FoldChange > 2.5 and adjusted P < 0.001) circular RNAs were shown. Six target microRNAs aligned with the top 14 circular RNAs were identified. According to the construction of the circular RNA-microRNA network and circBase information, only RNO_CIRCpedia_1775 had the homologous hsa_circ_0023826 in the human genome. The hsa_circ_0023826 and mRNA of the host gene TENM4 (teneurin transmembrane protein 4) were validated in aqueous humor samples of five glaucoma patients and five cataract control patients. The expression of hsa_circ_0023826 showed a significant decrease in glaucoma patients, while TENM4 mRNA showed no significant difference compared to cataract patients (P = 0.024 and P = 0.294, respectively). The results of this study comprehensively characterized the expression profiles of circular RNA in glaucoma-affected eyes, as verified by two different ocular hypertension rat models. Together with the target microRNAs underlying the top differentially expressed circular RNAs, a new target of hsa_circ_0023826 and its host gene TENM4 were identified and further verified in the aqueous humor of glaucoma patients, indicating a promising biomarker for the disease.

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Circular RNAs in rat models of cardiovascular and renal diseases.

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Circular RNAs in rat models of cardiovascular and renal diseases.

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