Profiles of Extracellular miRNAs in the Aqueous Humor of Glaucoma Patients Assessed with a Microarray System

Tanaka, Yuji; Tsuda, S.; Kunikata, Hiroshi; Sato, J.; Kokubun, Taiki; Yasuda, Masayuki; Nishiguchi, Koji M.; Inada, Toshifumi; Nakazawa, Toru

doi:10.1038/srep05089

Cited by 97 publications

(101 citation statements)

References 45 publications

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“…MicroRNAs play an important role in regulating the biological behavior of TM. [26][27][28] To determine the differential expression of miRNAs under oxidative stress, seven miRNAs, which may target the Smad family, were chosen, and the expression levels were detected by quantitative PCR (qPCR) (Fig. 2A).…”

Section: Mirnas Possibly Targeting Smad Family Are Downregulated In Hmentioning

confidence: 99%

MicroRNA-483-3p Inhibits Extracellular Matrix Production by Targeting Smad4 in Human Trabecular Meshwork Cells

Shen

Han

Huang

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. This study investigated the effects of microRNA-483-3p (miR-483-3p) on extracellular matrix (ECM) production, and clarified the regulatory mechanism of microRNA-483-3p in human trabecular meshwork cells (HTMCs) under oxidative stress. METHODS.The expression levels of ECM (fibronectin, laminin, collagen I) in HTMCs under oxidative stress were measured by Western blot. Changes of miR-483-3p expression in HTMCs were evaluated by quantitative polymerase chain reaction (qPCR). After using lentivirus stably expressing pri-miR-483, the effects of miR-483-3p on the ECM were assessed by qPCR and Western blot. Smad4, the potential target of miR-483-3p according to mRNA target-predicting algorithms, was confirmed by luciferase assay and Western blot. Furthermore, the effects of Smad4 knockdown on ECM expression were investigated by qPCR and Western blot.RESULTS. The mRNA and protein levels of ECM (fibronectin, laminin, collagen I) were upregulated in HTMCs induced by oxidative stress. The expression level of miR-483-3p decreased in HTMCs under oxidative stress, and the ectopic expression of miR-483-3p decreased the levels of ECM. In addition, miR-483-3p targeted Smad4 through two binding sites, resulting in a decrease of Smad4 expression. Furthermore, knockdown of Smad4 reduced the levels of ECM in HTMCs.CONCLUSIONS. MicroRNA-483-3p has an inhibitory effect on ECM production in HTMCs through downregulating Smad4, which indicates that miR-483-3p may serve as a potential therapeutic target in glaucoma.

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Section: Mirnas Possibly Targeting Smad Family Are Downregulated In Hmentioning

confidence: 99%

MicroRNA-483-3p Inhibits Extracellular Matrix Production by Targeting Smad4 in Human Trabecular Meshwork Cells

Shen

Han

Huang

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…7 MicroRNAs are expressed in various ocular tissues with a distinct tissue-specific and developmental stage-specific expression pattern, which suggests potential unique functions. 8 They have also been detected in ocular fluids 9 and have been implicated in human corneal diseases like keratoconus, 10 Fuchs' dystrophy, 11 and herpetic stromal keratitis. 12 Corneal inflammation in fungal keratitis poses a significant therapeutic challenge to clinicians, particularly because of the controversial role of corticosteroids in the initial disease management.…”

mentioning

confidence: 99%

Human Corneal MicroRNA Expression Profile in Fungal Keratitis

Hemadevi

Mohankumar

Lalitha

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. MicroRNAs (miRNAs) are small, stable, noncoding RNA molecules with regulatory function and marked tissue specificity that posttranscriptionally regulate gene expression. However, their role in fungal keratitis remains unknown. The purpose of this study was to identify the miRNA profile and its regulatory role in fungal keratitis. METHODS.Normal donor (n ¼ 3) and fungal keratitis (n ¼ 5) corneas were pooled separately, and small RNA deep sequencing was performed using a sequencing platform. A bioinformatics approach was applied to identify differentially-expressed miRNAs and their targets, and select miRNAs were validated by real-time quantitative PCR (qPCR). The regulatory functions of miRNAs were predicted by combining miRNA target genes and pathway analysis. The mRNA expression levels of select target genes were further analyzed by qPCR.RESULTS. By deep sequencing, 75 miRNAs were identified as differentially expressed with fold change greater than 2 and probability score greater than 0.9 in fungal keratitis corneas. The highly dysregulated miRNAs (miR-511-5p, miR-142-3p, miR-155-5p, and miR-451a) may regulate wound healing as they were predicted to specifically target wound inflammatory genes. Moreover, the increased expression of miR-451a in keratitis correlated with reduced expression of its target, macrophage migration inhibitory factor, suggesting possible regulatory functions.CONCLUSIONS. This is, to our knowledge, the first report on comprehensive human corneal miRNA expression profile in fungal keratitis. Several miRNAs with high expression in fungal keratitis point toward their potential role in regulation of pathogenesis. Further insights in understanding their role in corneal wound inflammation may help design new therapeutic strategies.

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“…The increased level of miR-24 by TGF-β 1 is essential to contain the TGF-β 1 levels during cyclic mechanical stress which is brought about by the targeting of furin by miR-24. Yet another study identified many miRNAs in glaucoma with Hsa-let-7b-3p as the most prevalent in aqueous humor [83]. miRNA profiles not only reveal the specific pathophysiology, but also offer the diagnosis.…”

Section: Mirnas and Eye Disordersmentioning

confidence: 99%

Micro-RNAs and Their Roles in Eye Disorders

Raghunath¹,

Perumal²

2015

Ophthalmic Res

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Micro-RNAs (miRNAs) are members of the family of noncoding RNA molecules that regulate gene expression by translational repression and mRNA degradation. Initial identification of miRNAs revealed them only as developmental regulators; later, their radiated roles in various cellular processes have been established. They regulate several pathways, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation and proliferation. Their roles in eye disorders are being explored by biologists around the world. Eye physiology requires the perfect orchestration of all the regulatory networks; any defect in any of the networks leads to eye disorders. The dysregulation of miRNA expression has been reported in many eye disorders, which paves the way for new therapeutics. This review summarizes the biogenesis of miRNAs and their role in eye disorders. miRNA studies also have implications for the understanding of various complex metabolic pathways leading to disorders of the eye. The ultimate understanding leads to potential opportunities in evaluating miRNAs as molecular biomarkers, prognostic tools, diagnostic tools and therapeutic agents for eye disorders.

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Profiles of Extracellular miRNAs in the Aqueous Humor of Glaucoma Patients Assessed with a Microarray System

Cited by 97 publications

References 45 publications

MicroRNA-483-3p Inhibits Extracellular Matrix Production by Targeting Smad4 in Human Trabecular Meshwork Cells

MicroRNA-483-3p Inhibits Extracellular Matrix Production by Targeting Smad4 in Human Trabecular Meshwork Cells

Human Corneal MicroRNA Expression Profile in Fungal Keratitis

Micro-RNAs and Their Roles in Eye Disorders

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