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Transcriptome analysis of common and diverged circulating miRNAs between arterial and venous during aging

ABSTRACT: Background: miRNAs derived from peripheral venous blood gained extensive attention as clinical biomarkers, while arterial miRNAs exhibited slightly different expression profiles. We compared the expression profiles of venous- and arterial-derived plasma miRNA between young and aged male SD rats by next-generation sequencing, in order to explore whether peripheral venous miRNAs can represent entire circulating vessels in abnormal conditions like aging. Results: MSigDB Hallmark Gene Set reference and TAM 2.0 server were used to investigate the enriched functions and associated diseases. The aging-related de-regulated miRNAs in artery and vein shown similar enriched functional terms. Of note, refer to the arterial-versus-venous differential-expressed miRNA profiles, only a few miRNAs shared between young and aged rats. Among them, miR-450a/b and miR-223 shown the similar tendency between young and aged rat, while miR-136 and miR-503 etc displayed the opposite direction under the same scenario. Since miRNAs are under the control of their specific transcriptional factors, we further analyzed upstream regulators which influence miRNAs level for vascular vessel location. TransmiR v2.0 tool was used and found enriched upstream transcription factors like NFκB and SIRT1. These transcriptional factors could be organ-specific expression and/or regulated in physiological and aging states as parts of plausible causal factors. Conclusion: This study screened and analyzed the differential differential-expressed miRNA profiles in arterial and venous plasma under aging conditions, suggesting the importance of origin of candidate circulating miRNA biomarkers upon the certain scenario and its potential regulatory rule.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE138317 | GEO | 2019/10/03

REPOSITORIES: GEO

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Project description:This SuperSeries is composed of the following subset Series: GSE24992: Drosophila brain microRNA expression with age: miRNA profiling GSE25007: Drosophila brain gene expression with age: mRNA profiling GSE25008: Drosophila brain gene expression between wildtype and miR-34 null flies Refer to individual Series. Aging is the most prominent risk factor for human neurodegenerative disease, but underlying mechanisms that connect two processes are less well characterized. With age, the brain undergoes functional decline and perhaps degeneration. Such decline may not just contribute to normal aging, but also enhance susceptibility to and progression of age-related neurodegenerative diseases. Therefore, defining intrinsic factors and pathways that underline the normal integrity of the adult nervous system may lead to insights that potentially link aging and neurodegeneration. Here, we report a highly conserved microRNA (miRNA), miR-34, as a modulator of aging and neurodegeneration. Using Drosophila, we show that fly miR-34 expression is brain-enriched and strikingly upregulated with age. Functional studies reveal that, whereas animals without miR-34 are normal as young adults, upon aging, they gradually show late-onset deficits characteristic of accelerated brain aging; these include a transcriptional signature of aged animals, coupled with rapid functional decline, loss of brain integrity, followed by a catastrophic decline in adult viability. Moreover, upregulation of miR-34 protects against neurodegeneration induced by pathogenic human polyglutamine (polyQ) disease protein. We next reveal a dramatic effect of miR-34 to silence the Eip74EF gene of steroid hormone pathways in the adult, which is crucial to maintain the normal aging. Collectively, these data define a miR-34-mediated mechanism that specifically affects long-term integrity of the adult nervous system. miR-34 function in Drosophila may thus present a link that functionally connects aging and neurodegeneration. Our studies implicate essential roles of miRNA- dependent pathways in maintenance of the adult brain, disease pathogenesis and healthy aging.

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Transcriptome analysis of common and diverged circulating miRNAs between arterial and venous during aging

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