Dataset Information

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

ABSTRACT: Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mouse model of oxygen-induced proliferative retinopathy (OIR). We found that miR-18a-5p was highly expressed in the retina of pups as well as retinal endothelial cells, and was consistently down-regulated during retinal development. On the other hand, miR-18a-5p was increased significantly during pathologic neovascularization in the retinas of OIR mice. Moreover, intravitreal administration of miRNA mimic, agomiR-18a-5p, significantly suppressed retinal neovascularization in OIR models. Accordingly, agomir-18a-5p markedly suppressed human retinal microvascular endothelial cell (HRMEC) function including proliferation, migration, and tube formation ability. Additionally, we demonstrated that miR-18a-5p directly down-regulated known vascular growth factors, fibroblast growth factor 1 (FGF1) and hypoxia-inducible factor 1-alpha (HIF1A), as the target genes. In conclusion, miR-18a-5p may be a useful drug target for pathologic ocular neovascularization.

SUBMITTER: Guan JT

PROVIDER: S-EPMC7076186 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

Guan Ji-Tian JT Li Xin-Xin XX Peng De-Wei DW Zhang Wen-Meng WM Qu Jia J Lu Fan F D'Amato Robert J RJ Chi Zai-Long ZL

Frontiers in pharmacology 20200310

Pathologic ocular neovascularization commonly results in visual impairment or even blindness in numerous fundus diseases, including proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and age-related macular degeneration (AMD). MicroRNAs regulate angiogenesis through modulating target genes and disease progression, making them a new class of targets for drug discovery. In this study, we investigated the potential role of miR-18a-5p in retinal neovascularization using a mo ...[more]

PMID: 32210827

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Project description:Purpose Clear cell renal cell carcinoma(ccRCC) is the most common type of renal cell carcinoma. While it is curable when detected at an early stage, some patients presented with advanced disease have poor prognosis. We aimed to identify key genes and miRNAs associated with clinical prognosis in ccRCC. Methods The microarray datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were analyzed by using GEO2R. Then, Functional enrichment analysis was performed using the DAVID. A retrospective series of 254 ccRCC patients with complete clinical information was included in this study. Kaplan-Meier analysis and multivariate cox regression analysis were used for prognostic analysis. Wound healing assay and transwell assay were designed to evaluate the migration and invasion ability of ccRCC cell lines. Results miRNA-18a was identified to be related with prognosis of ccRCC by using Kaplan-Meier analysis and multivariate cox regression analysis demonstrated that the prognostic value of miRNA-18a was independent of clinical features. Further studies showed that up-regulation of miRNA-18a had a positive effect on migration and invasion of ccRCC cells. The target gene (HIF1A) of the miRNA-18a was predicted by using the miRPathDB database. The transcription factors of DEGs were identified by using the i-cisTarget. Luckily, HIF1A was found to be one of the transcription factors of DEGs. Among these DEGs, PVT1 may be regulated by HIF1A and be related with prognosis of ccRCC. Finally, validation of miRNA18a/HIF1A/PVT1 pathway was checked via reverse transcription-polymerase chain reaction (RT-PCR) assay in both cell lines and clinical tumor samples. Conclusion Our research revealed that miRNA18a/HIF1A/PVT1 pathway might play a crucial role in ccRCC progression, providing novel insights into understanding of ccRCC molecular mechanisms. Importantly, miRNA-18a could serve as a potential diagnostic biomarker and therapeutic targets for ccRCC patients.

Dataset Information

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

Publications

MicroRNA-18a-5p Administration Suppresses Retinal Neovascularization by Targeting FGF1 and HIF1A.

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