Long Noncoding RNAs and Circular RNAs in Autoimmune Diseases

Lodde, Valeria; Murgia, Giampaolo; Simula, Elena Rita; Steri, Maristella; Floris, Matteo; Idda, Maria Laura

doi:10.3390/biom10071044

Cited by 94 publications

(66 citation statements)

References 162 publications

(207 reference statements)

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“…Meanwhile, correlations between circRIMS1 and clinical or pathological stages and histological grades will also be investigated. circRNAs have been reported to participate in the initiation and progression of sepsis, 43 schizophrenia, depression, 44 inflammatory bowel disease, 45 autoimmune diseases, 46 and especially human cancers. 47 , 48 , 49 , 50 , 51 , 52 Therefore, it is reasonable to speculate that they are also potential therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression

Wang

Fan

Cai

et al. 2020

Molecular Therapy - Nucleic Acids

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Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo . Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression

Wang

Fan

Cai

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Microglial proin ammatory states elicited by systemic immune responses to bacterial or viral pathogens are associated with a variety of neurodegenerative and autoimmune diseases (40)(41)(42)(43)(44). In order to determine whether inhibition of speci c molecular mechanisms regulating microglial-mediated neuroin ammation will be effective for prevention or treatment of these diseases, it is necessary to increase our understanding of the molecular processes regulating microglial proin ammatory states.…”

Section: Discussionmentioning

confidence: 99%

A novel long non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia.

Mathy

Burleigh

Kochvar

et al. 2020

Preprint

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Background Microglia are resident immunocompetent and phagocytic cells in the CNS. Pro-inflammatory microglia, stimulated by environmental microbial signals such as bacterial lipopolysaccharide (LPS), viral RNAs, or inflammatory cytokines, are neurotoxic and associated with pathogenesis of several neurodegenerative diseases. Long non-coding RNA (lncRNA) are emerging as important tissue-specific regulators directing cell differentiation and functional states and may help direct proinflammatory responses of microglia. Methods Microglial gene expression array analyses and qRT-PCR was used to identify a novel intergenic long-noncoding RNA that was upregulated in LPS-stimulated microglial cell lines, LPS-stimulated primary microglia, and LPS-injected mouse cortical tissue. Silencing and overexpression studies, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin RNA immunoprecipitation assays, and qRT-PCR were used to study the function of this long-noncoding RNA in microglia. In vitro cytotoxicity assays were used to examine the effects of silencing the novel long-noncoding RNA in LPS-stimulated microglia on neurotoxicity. Results We report here that the previously uncharacterized intergenic lncRNA we termed Nostrill is induced by LPS stimulation in both BV2 cells and primary murine microglia, as well as in cortical tissue of LPS-injected mice. Induction of Nostrill is NF-κB dependent and silencing of Nostrill decreased inducible nitric oxide synthase (iNOS) expression and nitric oxide production in BV2 and primary microglial cells. Overexpression of Nostrill increased iNOS expression and nitric oxide production. RNA immunoprecipitation assays demonstrated that Nostrill is physically associated with NF-κB subunit p65 following LPS stimulation. Silencing of Nostrill significantly reduced NF-κB p65 and RNA polymerase II recruitment to the iNOS promoter and decreased H3K4me3 activating histone modifications at iNOS gene loci. In vitro studies demonstrate that silencing of Nostrill in microglia reduced LPS-stimulated microglia neurotoxicity. Conclusions Our data indicate a new regulatory role of NF-κB-induced Nostrill and suggest that Nostrill acts as a co-activator of transcription of iNOS resulting in the production of nitric oxide in microglia through modulation of epigenetic chromatin remodeling. Nostrill may be a target for reducing the neurotoxicity associated with iNOS-mediated inflammatory processes in microglia during neurodegeneration.

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“…Taken together, these findings suggest that circRNAs may play a key role in the regulation of β-cell activity, and may be potentially involved in the pathogenesis of T1D and T2D. However, even if alteration in the expression of circRNAs have been demonstrated to play a role in the onset and/or progression of many autoimmune diseases [ 78 , 79 ], the potential contribution of circRNAs in T1D pathogenesis has been so far poorly investigated, especially in the β-cell context. Indeed, at present, the only evidence for a possible implication of circRNAs in T1D is the reduction in the expression of circARHGAP12 in the islets of pre-diabetic NOD mice, which spontaneously develop T1D [ 33 ].…”

Section: Circrnas In Pancreatic Islet Cellsmentioning

confidence: 98%

Circular RNAs as Novel Regulators of β-Cell Functions under Physiological and Pathological Conditions

Brozzi

Regazzi

2021

IJMS

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Circular RNAs (circRNAs) constitute a large class of non-coding RNAs characterized by a covalently closed circular structure. They originate during mRNA maturation through a modification of the splicing process and, according to the included sequences, are classified as Exonic, Intronic, or Exonic-Intronic. CircRNAs can act by sequestering microRNAs, by regulating the activity of specific proteins, and/or by being translated in functional peptides. There is emerging evidence indicating that dysregulation of circRNA expression is associated with pathological conditions, including cancer, neurological disorders, cardiovascular diseases, and diabetes. The aim of this review is to provide a comprehensive and updated view of the most abundant circRNAs expressed in pancreatic islet cells, some of which originating from key genes controlling the differentiation and the activity of insulin-secreting cells or from diabetes susceptibility genes. We will particularly focus on the role of a group of circRNAs that contribute to the regulation of β-cell functions and that display altered expression in the islets of rodent diabetes models and of type 2 diabetic patients. We will also provide an outlook of the unanswered questions regarding circRNA biology and discuss the potential role of circRNAs as biomarkers for β-cell demise and diabetes development.

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Long Noncoding RNAs and Circular RNAs in Autoimmune Diseases

Cited by 94 publications

References 162 publications

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression

Circular RNA circRIMS1 Acts as a Sponge of miR-433-3p to Promote Bladder Cancer Progression by Regulating CCAR1 Expression

A novel long non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia.

Circular RNAs as Novel Regulators of β-Cell Functions under Physiological and Pathological Conditions

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