Circular RNAs in diabetes and its complications: Current knowledge and future prospects

Yin, Wenfeng; Zhang, Ziwei; Xiao, Zilin; Li, Xia; Luo, Shuoming; Zhang, Zhou

doi:10.3389/fgene.2022.1006307

Cited by 9 publications

(7 citation statements)

References 151 publications

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“…The present study indicated that hsa_circRNA_100632 in PBMCs may be a diagnostic marker of FT1D. Increasing evidence has indicated that circRNAs may be diagnostic indicators of T1D and T2D (23). Hsa_circ_0054633, a diagnostic biomarker of prediabetes and T2D, shows diagnostic capability with AUC values of 0.751 and 0.793, respectively (24).…”

Section: Discussionsupporting

confidence: 50%

Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes

Yin

Luo²,

Qiu³

et al. 2023

Front. Immunol.

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ObjectiveCircular RNAs (circRNAs) are associated with diabetes, but their role in fulminant type 1 diabetes (FT1D) is unclear. Thus, we characterized the role of circRNAs in FT1D.Research design and methodsCircRNA expression profiles were detected in peripheral blood mononuclear cells (PBMCs) of five FT1D patients and five controls using a circRNA microarray. An independent cohort comprised of 40 FT1D cases, 75 type 1 diabetes (T1D) cases, and 115 controls was used to verify the circRNAs using quantitative real-time polymerase chain reaction (qRT-PCR). Spearman’s correlation analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the clinical diagnostic capability of circRNAs. Bioinformatics was used to identify potential biological functions and circRNA–miRNA–mRNA interactions.ResultsThere were 13 upregulated and 13 downregulated circRNAs in PBMCs of patients with FT1D. Five circRNAs were further verified in a second cohort. Hsa_circRNA_100632 was significantly upregulated in the FT1D and T1D groups. Hsa_circRNA_100632 was differentiated between patients with FT1D and controls [area under the curve (AUC) 0.846; 95% CI 0.776–0.916; P<0.0001] as well as between patients with FT1D and patients with T1D (AUC 0.726; 95% CI 0.633–0.820; P<0.0001). Bioinformatics analysis showed that hsa_circRNA_100632 may be involved in 47 circRNA–miRNA–mRNA signaling pathways associated with diabetes.ConclusionsCircRNAs were aberrantly expressed in PBMCs of patients with FT1D, and hsa_circRNA_100632 may be a diagnostic marker of FT1D.

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Section: Discussionsupporting

confidence: 50%

Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes

Yin

Luo²,

Qiu³

et al. 2023

Front. Immunol.

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“…In the past decades, circRNAs have been reported to mediate human diseases such as neurological diseases, cardiovascular diseases, and cancer (10)(11)(12)(13)(14)(15)(16)(17). The expression, regulation, function, and mechanisms of circRNAs in the development of inflammatory lung responses have not been studied.…”

Section: Discussionmentioning

confidence: 99%

“…Circular RNA has been linked to some diseases such as cancer ( 10 ), diabetes ( 11 ), cardiovascular diseases ( 12 ), age-related diseases ( 13 ), osteoarthritis ( 14 ), stress ( 15 ), and viral diseases ( 16 , 17 ). Due to the lack of 5’ or 3’ ends and resistance to exonuclease-mediated degradation, circRNAs are presumably more stable than most linear RNA in cells, tissues, and body fluids ( 1 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

Altered circular RNA expressions in extracellular vesicles from bronchoalveolar lavage fluids in mice after bacterial infections

Lee,

Hong,

Jin

2024

Front. Immunol.

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Circular RNAs (circRNAs) are a class of transcripts that often are generated by back-splicing that covalently connects the 3′end of the exon to the 5′end. CircRNAs are more resistant to nuclease and more stable than their linear counterparts. One of the well-recognized roles of circRNAs is the miRNA sponging effects that potentially lead to the regulation of downstream proteins. Despite that circRNAs have been reported to be involved in a wide range of human diseases, including cancers, cardiovascular, and neurological diseases, they have not been studied in inflammatory lung responses. Here, we analyzed the circRNA profiles detected in extracellular vesicles (EVs) obtained from the broncho-alveolar lavage fluids (BALF) in response to LPS or acid instillation in mice. Next, we validated two specific circRNAs in the BALF-EVs and BALF cells in response to endotoxin by RT-qPCR, using specific primers targeting the circular form of RNAs rather than the linear host RNAs. The expression of these selected circRNAs in the BALF inflammatory cells, alveolar macrophages (AMs), neutrophils, and lung tissue were analyzed. We further predicted the potential miRNAs that interact with these circRNAs. Our study is the first report to show that circRNAs are detectable in BALF EVs obtained from mice. The EV-cargo circRNAs are significantly altered by the noxious stimuli. The circRNAs identified using microarrays may be validated by RT-qPCR using primers specific to the circular but not the linear form. Future studies to investigate circRNA expression and function including miRNA sponging in lung inflammation potentially uncover novel strategies to develop diagnostic/therapeutic targets.

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“…They are mainly released by active secretion in extracellular vesicles or by binding to proteins such as high-density lipo-proteins (HDLs), apoptotic bodies, and micro-particles [ 5 ]. Circulating microRNAs (miRNAs) have been suggested as biomarkers for a number of conditions and have been shown to be important in a number of inflammatory-mediated processes [ 6 , 7 ], including asthma [ 8 ]. We hypothesized that circulating miRNA in serum would be associated with ICS response in children with asthma.…”

Section: Introductionmentioning

confidence: 99%

Systems Genomics Reveals microRNA Regulation of ICS Response in Childhood Asthma

Sharma

Tiwari

Kho

et al. 2023

Cells

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Background: Asthmatic patients’ responses to inhaled corticosteroids (ICS) are variable and difficult to quantify. We have previously defined a Cross-sectional Asthma STEroid Response (CASTER) measure of ICS response. MicroRNAs (miRNAs) have shown strong effects on asthma and inflammatory processes. Objective: The purpose of this study was to identify key associations between circulating miRNAs and ICS response in childhood asthma. Methods: Small RNA sequencing in peripheral blood serum from 580 children with asthma on ICS treatment from The Genetics of Asthma in Costa Rica Study (GACRS) was used to identify miRNAs associated with ICS response using generalized linear models. Replication was conducted in children on ICS from the Childhood Asthma Management Program (CAMP) cohort. The association between replicated miRNAs and the transcriptome of lymphoblastoid cell lines in response to a glucocorticoid was assessed. Results: The association study on the GACRS cohort identified 36 miRNAs associated with ICS response at 10% false discovery rate (FDR), three of which (miR-28-5p, miR-339-3p, and miR-432-5p) were in the same direction of effect and significant in the CAMP replication cohort. In addition, in vitro steroid response lymphoblastoid gene expression analysis revealed 22 dexamethasone responsive genes were significantly associated with three replicated miRNAs. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) revealed a significant association between miR-339-3p and two modules (black and magenta) of genes associated with immune response and inflammation pathways. Conclusion: This study highlighted significant association between circulating miRNAs miR-28-5p, miR-339-3p, and miR-432-5p and ICS response. miR-339-3p may be involved in immune dysregulation, which leads to a poor response to ICS treatment.

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Circular RNAs in diabetes and its complications: Current knowledge and future prospects

Cited by 9 publications

References 151 publications

Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes

Identification of hsa_circRNA_100632 as a novel molecular biomarker for fulminant type 1 diabetes

Altered circular RNA expressions in extracellular vesicles from bronchoalveolar lavage fluids in mice after bacterial infections

Systems Genomics Reveals microRNA Regulation of ICS Response in Childhood Asthma

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