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环状 RNA HIPK3 通过海绵吸附多个 microRNAs 介导视网膜色素上皮细胞的上皮-间充质转化。

Circular RNA HIPK3 mediates epithelial-mesenchymal transition of retinal pigment epithelial cells by sponging multiple microRNAs.

机构信息

Department of Ophthalmology, Yixing Eye Hospital, Wuxi School of Medicine, Jiangnan University, Intersection of Hongta Road Kang Ming Road, Yicheng Street, Yixing, 214200, Jiangsu, China.

Shanghai Eye Diseases Prevention & Treatment Center, Shanghai, China.

出版信息

Sci Rep. 2024 Nov 21;14(1):28872. doi: 10.1038/s41598-024-71119-6.

DOI:10.1038/s41598-024-71119-6
PMID:39572643
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11582593/
Abstract

Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells plays key roles in the pathogenesis of multiple vitreoretinal diseases, leading to profound and permanent vision loss. Circular RNAs (circRNAs) are widespread and functional endogenous RNAs that could regulate gene expression in eukaryotes. The functions of circRNAs in mediating EMT has been reported in several diseases. In the current study, we investigated the role of circRNA HIPK3 (circHIPK3) in EMT process of RPE cells (RPE-EMT). circHIPK3 is one abundant circRNA generated from the second exon of HIPK3 mRNA. We found that circHIPK3 expression was significantly increased in TGF-β1-induced RPE-EMT model. Silencing of circHIPK3 attenuated TGF-β1-induced RPE-EMT process, whereas forced expression of circHIPK3 could trigger EMT in RPE cells. Mechanistically, circHIPK3 regulates RPE-EMT process via sponging multiple microRNAs (miRNAs). This study provides novel insights into the mechanism of RPE-EMT. Targeting circHIPK3 might serve as a therapeutic strategy in RPE-EMT associated vitreoretinal diseases.

摘要

上皮-间充质转化 (EMT) 是视网膜色素上皮 (RPE) 细胞在多种眼后段疾病发病机制中的关键作用，导致深刻和永久性的视力丧失。环状 RNA (circRNA) 是广泛存在且具有功能的内源性 RNA，可在真核生物中调节基因表达。circRNA 在介导 EMT 中的作用已在多种疾病中得到报道。在本研究中，我们研究了 circRNA HIPK3 (circHIPK3) 在 RPE 细胞 EMT 过程中的作用 (RPE-EMT)。circHIPK3 是由 HIPK3 mRNA 的第二个外显子产生的一种丰富的 circRNA。我们发现，circHIPK3 在 TGF-β1 诱导的 RPE-EMT 模型中表达显著增加。circHIPK3 的沉默减弱了 TGF-β1 诱导的 RPE-EMT 过程，而 circHIPK3 的强制表达可引发 RPE 细胞 EMT。机制上，circHIPK3 通过海绵吸附多个 microRNAs (miRNAs) 来调节 RPE-EMT 过程。本研究为 RPE-EMT 的机制提供了新的见解。靶向 circHIPK3 可能成为 RPE-EMT 相关眼后段疾病的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/dc5b2f0a10b9/41598_2024_71119_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/e44ee27e5c9f/41598_2024_71119_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/c2c7ce9f075c/41598_2024_71119_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/b67b9dd8f2a3/41598_2024_71119_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/b3911b9e035c/41598_2024_71119_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/dc5b2f0a10b9/41598_2024_71119_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/e44ee27e5c9f/41598_2024_71119_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/c2c7ce9f075c/41598_2024_71119_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/b67b9dd8f2a3/41598_2024_71119_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/b3911b9e035c/41598_2024_71119_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38e2/11582593/dc5b2f0a10b9/41598_2024_71119_Fig5_HTML.jpg

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