Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens–Johnson syndrome in the chronic stage

Ueta, Mayumi; Nishigaki, H; Sotozono, Chie; Yokoi, Norihiko; Mizushima, Katsura; Naito, Yuji; Kinoshita, Shigeru

doi:10.1038/s41598-020-74211-9

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…Affymetrix GeneChip miRNA 4.0 arrays were used for miRNA profiling. Total RNA was labeled with the FlashTag ™ Biotin HSR RNA labeling kit (Affymetrix, Inc., USA) (Ueta et al, 2020;Ueta et al, 2021a). The samples were hybridized on GeneChip miRNA 4.0 arrays (Affymetrix) for 18 h at 48 °C.…”

Section: Microarray Profiling Of Mirnasmentioning

confidence: 99%

Positive regulation of innate immune response by miRNA-let-7a-5p

Ueta¹,

Nishigaki²,

Komai³

et al. 2023

Front. Genet.

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Background: We have hypothesized that different factors are involved in the severity of ACD and AD because some but not all patients with atopic dermatitis (AD) present with allergic conjunctival disease (ACD) including severe types such as atopic keratoconjunctivitis (AKC) with/without giant papillae. We previously reported that plasma miR-628-3p was up-regulated in AD with severe ACD, but not in severe AD without severe ACD or in our healthy controls. In this study, to investigate the pathogenesis of AD with and without severe ACD, we performed comprehensive plasma miRNA analysis and studied the function of some miRNAs which were significantly up-regulated in ACD.Methods: Transcriptomics analysis of miRNA was performed using the microarray platform from the plasma of nine individuals (AD, severe ACD, controls: n = 3 each). To confirm up-regulation of the 12 miRNAs of the eight miRNA groups we focused on, we performed quantitative miRNA polymerase chain reaction (PCR) assays using 80 plasma samples (AD: 23, severe ACD: 17, controls: 40). To study the function of the eight miRNAs which were significantly up-regulated in ACD, we transfected their mimic to THP-1 cells, a monocyte cell line, and performed comprehensive gene expression analysis of them. The up-regulation of gene expression of interest in transfected THP-1 cells with the hsa-let-7a-5p miRNA mimic was confirmed by quantitative RT-qPCR assay.Results: Quantitative miRNA PCR assays showed that hsa-let-7a-5p, hsa-let-7days-3p, hsa-let-7e-5p, and hsa-miR-151a-5p were significantly up-regulated in both AD-ACD+ and AD-ACD- as were hsa-miR-130a-3p, hsa-miR-151a-3p, has-miR-27b-3p, and hsa-miR-146a-5p in AD-ACD+ but not in AD-ACD-. The functions of each miRNA were investigated by comprehensive gene expression analysis of THP-1 cells transfected with each miRNA mimic. Of the eight miRNAs, hsa-let-7a-5p, hsa-let-7e-5p, has-miR-27b-3p, and hsa-miR-146a-5p mimic-transfected THP-1 cells showed the up-regulation of CXCL10 (IP-10; interferon gamma-induced protein 10), which might be one of the innate immune-related genes. Quantitative RT-qPCR assays of transfected THP-1 cells with the hsa-let-7a-5p miRNA mimic showed that the 17 genes up-regulated more than 10-fold in the comprehensive gene expression analysis, and TLR3, RIG-I, and MDA5, important innate immune-related genes, were significantly up-regulated. TNFSF13B, AIM2, USP41, STAP1, GBP4, CCL8, and IFI27, reportedly down-regulated by the hsa-miR-628-3p mimic, were also significantly up-regulated in the transfected cells.Conclusion: Hsa-let-7a-5p, which was significantly up-regulated in AD-ACD+ and AD-ACD-, could positively regulate the important innate immune-related genes such as TLR3, RIG-I, and MDA5. It is possible that in an allergic disease such as atopic keratoconjunctivitis and/or dermatitis, innate immune responses might be positively regulated by hsa-let-7a-5p in the plasma.

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Section: Microarray Profiling Of Mirnasmentioning

confidence: 99%

Positive regulation of innate immune response by miRNA-let-7a-5p

Ueta¹,

Nishigaki²,

Komai³

et al. 2023

Front. Genet.

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“…The expression of miR-18a-5p, miR-124 and miR-375-3p were up-regulated in various cells and body fluids [68][69][70]. Ueta et al (2020) investigated the role of miRNAs in the pathogenesis of SJS/TEN patients with SOC. The expression of miR-31 and miR-455-3p is shown to be significantly up-regulated in the conjunctival epithelium of SJS/TEN chronic patients.…”

Section: F) Steven-johnson Syndromementioning

confidence: 99%

“…The expression of miR-31 and miR-455-3p is shown to be significantly upregulated in the conjunctival epithelium of SJS/ TEN chronic patients. It was further reported that the miR-455-3p regulates many innate immune related genes in human conjunctival epithelium [ 50 ].…”

Section: Role Of Mirnas In the Conjunctival Disordersmentioning

confidence: 99%

MicroRNA and Their Potential Role in Conjunctival Disorders

Syed

Shatriah

Zunaina

et al. 2022

Korean J Ophthalmol

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MicroRNAs (miRNAs) are the small non-coding RNA molecules which regulate target gene expression post-transcriptionally. They are known to regulate key cellular processes like inflammation, cell differentiation, cell proliferation and cell apoptosis across various ocular diseases. Due to their easier access, recent focus has been laid on the investigation of miRNA expression and their involvement in several conjunctival diseases. The aim of this narrative review is to provide understanding of the miRNAs and describe the current role of miRNAs as the mediators of the various conjunctival diseases. A literature search was made using PubMed, Scopus and Web of Science databases for studies involving miRNAs in the conjunctival pathological conditions. Original articles in the last 10 years involving both human and animal models were included. Literature search retrieved 27 studies matching our criteria.Pertaining to the numerous literatures, there is a strong correlation between miRNA and the various pathological conditions that occur in the conjunctiva. MiRNAs are involved in various physiological processes such as cell differentiation, proliferation, apoptosis, development, and inflammation by regulating various signaling pathways, genes, proteins, and mediators. Pterygium was the most studied conjunctival disease for miRNA involvement, whereas miRNA research in allergic conjunctivitis is still in its early stages. Our review provides deep insights into the various miRNAs playing an important role in the various conjunctival diseases. MiRNAs do have the potential to serve as non-invasive biomarkers with diagnostic, prognostic, and therapeutic implications. However, multitudinous studies are required to validate miRNAs as the reliable biomarkers in conjunctival pathologies and its targeted therapy.

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“…Indeed, reducing Ankrd1 protein levels has been demonstrated to prevent development of dilated cardiomyopathy in mice (Lange et al 2016 ). A recent study found that Ankrd1 mRNA levels could be downregulated by inhibiting miR-455-3p (Ueta et al 2020 ), a miRNA that was linked to worsened hypertrophic remodeling in mice that underwent pressure overload by transverse aortic constriction (TAC) (Wu et al 2015 ). However, it is unclear if the mouse version of miR-455 targets Ankrd1 mRNA, as the sequences show poor evolutionary conservation between mice and humans.…”

Section: The Emerging Therapeutic Potential Of Modulating Titin I-band Splicing and Phosphorylation As Well As Titin-associated Proteinsmentioning

confidence: 99%

The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles

et al. 2021

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Muscle specific signaling has been shown to originate from myofilaments and their associated cellular structures, including the sarcomeres, costameres or the cardiac intercalated disc. Two signaling hubs that play important biomechanical roles for cardiac and/or skeletal muscle physiology are the N2B and N2A regions in the giant protein titin. Prominent proteins associated with these regions in titin are chaperones Hsp90 and αB-crystallin, members of the four-and-a-half LIM (FHL) and muscle ankyrin repeat protein (Ankrd) families, as well as thin filament-associated proteins, such as myopalladin. This review highlights biological roles and properties of the titin N2B and N2A regions in health and disease. Special emphasis is placed on functions of Ankrd and FHL proteins as mechanosensors that modulate muscle-specific signaling and muscle growth. This region of the sarcomere also emerged as a hotspot for the modulation of passive muscle mechanics through altered titin phosphorylation and splicing, as well as tethering mechanisms that link titin to the thin filament system.

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Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens–Johnson syndrome in the chronic stage

Cited by 7 publications

References 36 publications

Positive regulation of innate immune response by miRNA-let-7a-5p

Positive regulation of innate immune response by miRNA-let-7a-5p

MicroRNA and Their Potential Role in Conjunctival Disorders

The titin N2B and N2A regions: biomechanical and metabolic signaling hubs in cross-striated muscles

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