circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan

Haque, Syed Ehtaishamul; Ames, Ryan M.; Moore, Karen; Pilling, Luke C.; Peters, Luanne L.; Bandinelli, Stefania; Ferrucci, Luigi; Harries, Lorna W.

doi:10.1007/s11357-019-00120-z

Cited by 45 publications

(43 citation statements)

References 57 publications

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“…For our initial description of the islet circRNome, we generated circular RNA profiles from a pooled sample consisting of 5 individual islet preparations from donors without T2D using a modified 'CircleSeq' procedure [20] as in our previous work [21]. Samples were derived from 3 females and 2 males, with an average age of 50.2 years and an average BMI of 26.4, and were pooled to prevent any bias arising from signals arising from single donors.…”

Section: Generation Of Human Primary Islet Circrna Profilementioning

confidence: 99%

“…Islet preparations had, an average viability 94.4% and an average purity of 81%. CircRNA sequencing was carried out as previously published [21]. Sixty-two M reads were obtained from the RNase R-treated sample and 41 M reads from the mocktreated sample.…”

Section: Generation Of Human Primary Islet Circrna Profilementioning

confidence: 99%

“…The mean Q score was 38.9-39.1 and the total error rate was 0.24%. CircRNA sequences were then determined and quantified as in our previous work [21].…”

Section: Generation Of Human Primary Islet Circrna Profilementioning

confidence: 99%

“…To determine whether circRNAs identified were derived from genes clustered into specific gene ontology pathways, we carried out an initial gene set enrichment GSE analysis using the ClueGO Cytoscape version 2.5.2 plug-in (Bindea et al, 2009), as described in our previous work [21].…”

Section: Pathway Analysis Of Genes Hosting Differentially-regulated Cmentioning

confidence: 99%

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Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood

et al. 2020

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Background: Circular RNAs are non-coding RNA molecules with gene regulatory potential that have been associated with several human diseases. They are stable and present in the circulation, making them excellent candidates for biomarkers of disease. Despite their promise as biomarkers or future therapeutic targets, information on their expression and functionality in human pancreatic islets is a relatively unexplored subject. Methods: Here we aimed to produce an enriched circRNAome profile for human pancreatic islets by CircleSeq, and to explore the relationship between circRNA expression, diabetes status, genotype at T2D risk loci and measures of glycaemia (insulin secretory index; SI and HbA1c) in human islet preparations from healthy control donors and donors with type 2 diabetes using ANOVA or linear regression as appropriate. We also assessed the effect of elevated glucose, cytokine and lipid and hypoxia on circRNA expression in the human beta cell line EndoC-βH1. Results: We identified over 2600 circRNAs present in human islets. Of the five most abundant circRNAs in human islets, four (circCIRBP, circZKSCAN, circRPH3AL and circCAMSAP1) demonstrated marked associations with diabetes status. CircCIRBP demonstrated an association with insulin secretory index in isolated human islets and circCIRBP and circRPH3AL displayed altered expression with elevated fatty acid in treated EndoC-βH1 cells. CircCAMSAP1 was also noted to be associated with T2D status in human peripheral blood. No associations between circRNA expression and genotype at T2D risk loci were identified in our samples. Conclusions: Our data suggest that circRNAs are abundantly expressed in human islets, and that some are differentially regulated in the islets of donors with type 2 diabetes. Some islet circRNAs are also expressed in peripheral blood and the expression of one, circCAMSAP1, correlates with diabetes status. These findings highlight the potential of circRNAs as biomarkers for T2D.

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Section: Generation Of Human Primary Islet Circrna Profilementioning

confidence: 99%

Section: Generation Of Human Primary Islet Circrna Profilementioning

confidence: 99%

“…The mean Q score was 38.9-39.1 and the total error rate was 0.24%. CircRNA sequences were then determined and quantified as in our previous work [21].…”

Section: Generation Of Human Primary Islet Circrna Profilementioning

confidence: 99%

Section: Pathway Analysis Of Genes Hosting Differentially-regulated Cmentioning

confidence: 99%

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Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood

et al. 2020

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“…CircRNA profiles in aged human peripheral blood not only provide epidemiological evidence for a role in human aging phenotypes, or lifespan, but also in vitro evidence that some circRNA may influence cell senescence phenotypes [115]. In stress related pathways, circ-FOXO3 plays an important role as its dysregulation results in sequestration of various proteins.…”

Section: Circrna In Stress and Senescencementioning

confidence: 99%

Deep Insights in Circular RNAs: from biogenesis to therapeutics

et al. 2020

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Circular RNAs (circRNAs) have emerged as a universal novel class of eukaryotic non-coding RNA (ncRNA) molecules and are becoming a new research hotspot in RNA biology. They form a covalent loop without 5′ cap and 3′ tail, unlike their linear counterparts. Endogenous circRNAs in mammalian cells are abundantly conserved and discovered so far. In the biogenesis of circRNAs exonic, intronic, reverse complementary sequences or RNA-binding proteins (RBPs) play a very important role. Interestingly, the majority of them are highly conserved, stable, resistant to RNase R and show developmental-stage/tissue-specific expression. CircRNAs play multifunctional roles as microRNA (miRNA) sponges, regulators of transcription and post-transcription, parental gene expression and translation of proteins in various diseased conditions. Growing evidence shows that circRNAs play an important role in neurological disorders, atherosclerotic vascular disease, and cancer and potentially serve as diagnostic or predictive biomarkers due to its abundance in various biological samples. Here, we review the biogenesis, properties, functions, and impact of circRNAs on various diseases.

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Cellular senescence: A potential mode of circular RNAs regulating prostate cancer

Li,

Fan,

Zhang

et al. 2023

MedComm – Oncology

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Cellular senescence is a state characterized by permanent cell cycle stoppage, which has long been viewed as a protective mechanism against neoplasia. However, accumulating evidence reveal that cellular senescence variously stimulates tumorigenesis and malignant progression in certain contexts. Senescence‐associated secretory phenotype (SASP) is a crucial feature of senescent cells and the main way they function. Prostate cancer (PCa) is apparently an age‐related tumor with a high prevalence in the elderly. With the aggravation of population aging the morbidity of PCa continues to rise. And with the progress of the disease, most patients eventually develop castration‐resistant PCa (CRPC) or drug resistance, which poses a challenge for the treatment of PCa and aggravates the burden on patients and society. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs formed by back‐splicing of pre‐mRNAs. Characterized by special covalently closed circular structure, they play important regulatory roles in various tumors. Numerous studies have revealed that circRNAs can regulate PCa and cellular senescence in diverse ways. This review explores a potential mode that circRNAs regulate PCa, reveales a significant mechanism of tumorigenesis and progression for PCa, suggesting a new strategy for PCa research.

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circRNAs expressed in human peripheral blood are associated with human aging phenotypes, cellular senescence and mouse lifespan

Cited by 45 publications

References 57 publications

Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood

Islet-expressed circular RNAs are associated with type 2 diabetes status in human primary islets and in peripheral blood

Deep Insights in Circular RNAs: from biogenesis to therapeutics

Cellular senescence: A potential mode of circular RNAs regulating prostate cancer

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