Circular RNAs: Novel Players in the Oxidative Stress‐Mediated Pathologies, Biomarkers, and Therapeutic Targets

Wang, Yunguang; He, Wenfang; Ibrahim, Sherif A.; He, Qiang; Jin, Juan

doi:10.1155/2021/6634601

Cited by 9 publications

(6 citation statements)

References 89 publications

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“…One fundamental mechanism of action of circRNAs is mediated by their ability to bind and sponge out specific miRNAs, therefore regulating the expression of their target mRNAs. Mounting evidence has indicated the dysregulation of the circRNA–miRNA–mRNA interaction network in the pathogenesis of many diseases [ 51 ], including oxidative stress-mediated pathologies [ 21 , 52 , 53 ]. To reveal potential interaction networks of circANKRD12 triggered by oxidative stress in ECs, we designed two pipelines using online prediction tools and the dataset of transcriptomic changes induced by H 2 O 2 treatment in HUVEC cells we had previously published [ 5 ].…”

Section: Resultsmentioning

confidence: 99%

CircANKRD12 Is Induced in Endothelial Cell Response to Oxidative Stress

Voellenkle

Fuschi

Mutoli

et al. 2022

Cells

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Redox imbalance of the endothelial cells (ECs) plays a causative role in a variety of cardiovascular diseases. In order to better understand the molecular mechanisms of the endothelial response to oxidative stress, the involvement of circular RNAs (circRNAs) was investigated. CircRNAs are RNA species generated by a "back-splicing" event, which is the covalent linking of the 3'- and 5'-ends of exons. Bioinformatics analysis of the transcriptomic landscape of human ECs exposed to H2O2 allowed us to identify a subset of highly expressed circRNAs compared to their linear RNA counterparts, suggesting a potential biological relevance. Specifically, circular Ankyrin Repeat Domain 12 (circANKRD12), derived from the junction of exon 2 and exon 8 of the ANKRD12 gene (hsa_circ_0000826), was significantly induced in H2O2-treated ECs. Conversely, the linear RNA isoform of ANKRD12 was not modulated. An increased circular-to-linear ratio of ANKRD12 was also observed in cultured ECs exposed to hypoxia and in skeletal muscle biopsies of patients affected by critical limb ischemia (CLI), two conditions associated with redox imbalance and oxidative stress. The functional relevance of circANKRD12 was shown by the inhibition of EC formation of capillary-like structures upon silencing of the circular but not of the linear isoform of ANKRD12. Bioinformatics analysis of the circANKRD12–miRNA–mRNA regulatory network in H2O2-treated ECs identified the enrichment of the p53 and Foxo signaling pathways, both crucial in the cellular response to redox imbalance. In keeping with the antiproliferative action of the p53 pathway, circANKRD12 silencing inhibited EC proliferation. In conclusion, this study indicates circANKRD12 as an important player in ECs exposed to oxidative stress.

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Section: Resultsmentioning

confidence: 99%

CircANKRD12 Is Induced in Endothelial Cell Response to Oxidative Stress

Voellenkle

Fuschi

Mutoli

et al. 2022

Cells

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“…These were affected by mRNAs like Atp6v0a1, Atp6v0b, Atp6v0c, and Atp6v0e2 which were then involved in the miRNA-circRNA interaction network involved in the progression of the Nrf-2 mediated development of RA. 134 The effect of circRNA is extremely underlying and has far reaching effect on the progression of the disease. Recent research has verified that epigenetically regulated gene networks in the peripheral blood mononuclear cells consequently result in the severity regulation of RA.…”

Section: Ramentioning

confidence: 99%

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Nag,

Mitra,

Tripathi

et al. 2023

Immunity Inflam & Disease

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BackgroundAutoimmune diseases (AD) are severe pathophysiological ailments that are stimulated by an exaggerated immunogenic response towards self‐antigens, which can cause systemic or site‐specific organ damage. An array of complex genetic and epigenetic facets majorly contributes to the progression of AD, thus providing significant insight into the regulatory mechanism of microRNA (miRNA). miRNAs are short, non‐coding RNAs that have been identified as essential contributors to the post‐transcriptional regulation of host genome expression and as crucial regulators of a myriad of biological processes such as immune homeostasis, T helper cell differentiation, central and peripheral tolerance, and immune cell development.AimsThis article tends to deliberate and conceptualize the brief pathogenesis and pertinent epigenetic regulatory mechanism as well as miRNA networks majorly affecting five different ADs namely rheumatoid arthritis (RA), type 1 diabetes, multiple sclerosis (MS), systemic lupus erythematosus (SLE) and inflammatory bowel disorder (IBD) thereby providing novel miRNA‐based theranostic interventions.Results & DiscussionPertaining to the differential expression of miRNA attributed in target tissues and cellular bodies of innate and adaptive immunity, a paradigm of scientific expeditions suggests an optimistic correlation between immunogenic dysfunction and miRNA alterations.ConclusionTherefore, it is not astonishing that dysregulations in miRNA expression patterns are now recognized in a wide spectrum of disorders, establishing themselves as potential biomarkers and therapeutic targets. Owing to its theranostic potencies, miRNA targets have been widely utilized in the development of biosensors and other therapeutic molecules originating from the same.

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“…Stability, unlike linear RNA, circRNAs is a single-stranded, covalent closed-loop structure without a 5′ cap structure and a 3′ terminal ploy(A) tail. This structure may protect it from degradation by RNA exonuclease (RNAser) and thus has higher stability than linear RNA ( Suzuki and Tsukahara, 2014 ; Di Timoteo et al, 2020 ; Wang et al, 2021h ). Conservative, circRNAs is highly conserved across species ( AbouHaidar et al, 2014 ; Mao et al, 2021 ; Meyer et al, 2021 ).…”

Section: Biogenesis and Classification Of Circular Rnasmentioning

confidence: 99%

“…Studies have shown that circRNAs are abundant and stable in exosomes, and some circRNAs are more highly expressed in blood than in tissues ( D'Ambrosi et al, 2021 ; Reese and Dhayat, 2021 ; Tian et al, 2021 ; van Zonneveld et al, 2021 ). The high expression and stability of circRNAs in body fluids would be more beneficial for their clinical applications ( Bu et al, 2021 ; Fontemaggi et al, 2021 ; Wang et al, 2021h ; Zhao et al, 2021 ). However, despite the identification of thousands of tissue- and disease-specific circRNAs by RNA-seq ( Kaushik et al, 2021 ; Tian-Zhao et al, 2021 ), the understanding of the mechanism of circRNAs generation and biological functions is limited at this stage.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Research Progress of circRNAs in Glioblastoma

Guo

Piao

2021

Front. Cell Dev. Biol.

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Circular RNAs (circRNAs) are a class of single-stranded covalently closed non-coding RNAs without a 5′ cap structure or 3′ terminal poly (A) tail, which are expressed in a variety of tissues and cells with conserved, stable and specific characteristics. Glioblastoma (GBM) is the most aggressive and lethal tumor in the central nervous system, characterized by high recurrence and mortality rates. The specific expression of circRNAs in GBM has demonstrated their potential to become new biomarkers for the development of GBM. The specific expression of circRNAs in GBM has shown their potential as new biomarkers for GBM cell proliferation, apoptosis, migration and invasion, which provides new ideas for GBM treatment. In this paper, we will review the biological properties and functions of circRNAs and their biological roles and clinical applications in GBM.

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Circular RNAs: Novel Players in the Oxidative Stress‐Mediated Pathologies, Biomarkers, and Therapeutic Targets

Cited by 9 publications

References 89 publications

CircANKRD12 Is Induced in Endothelial Cell Response to Oxidative Stress

CircANKRD12 Is Induced in Endothelial Cell Response to Oxidative Stress

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

Research Progress of circRNAs in Glioblastoma

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