Long Non-Coding RNA PNKY Modulates the Development of Choroidal Neovascularization.
Long Non-Coding RNA PNKY Modulates the Development of Choroidal Neovascularization.
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DOI：
10.3389/fcell.2022.836031
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发表时间：
2022
影响因子：
5.5
通讯作者：
Yao J
中科院分区：
文献类型：
--
作者：
Shi L;Han X;Liu C;Li X;Lu S;Jiang Q;Yao J
长链非编码RNA（lncRNA）在人类疾病中有着广泛的应用。我们的目的是探讨PNKY表达水平的变化及其相关信号网络在介导应激诱导的脉络膜新生血管中的调节作用。激光和缺氧应激可降低内皮细胞PNKY表达水平。在激光诱导的CNV模型和离体模型中，PNKY沉默加剧了CNV的形成，而过表达抑制了CNV的发展。PNKY的沉默或过表达改变了体外内皮细胞的活力、增殖、迁移和管形成能力。在机制上，通过lncRNA-RNA结合蛋白-miRNA相互作用分析，包括功能丧失和功能获得实验，我们发现lncRNAPNKY抑制miR 124与PTBP 1的结合，并通过促进Bcl-2样蛋白11（BIM）来维持脉络膜血管功能的稳态，其功能障碍导致CNV病变加重。因此，本研究提示lncPNKY/PTBP 1-miR-124轴参与调控CNV的发生发展，为CNV的治疗提供了潜在的治疗靶点。
Long non-coding RNAs (lncRNAs) have been widely implicated in human diseases. Our aim was to explore the regulatory role of changes in the expression levels of PNKY and its linked signaling networks in mediating stress-induced choroidal neovascularization. PNKY expression levels were reduced in mice by laser and exposure of endothelial cell to hypoxic stress. PNKY silencing exacerbated the formation of CNV in a laser-induced CNV model and an ex vivo model, while overexpression inhibited CNV development. Silencing or overexpression of PNKY altered the viability, proliferation, migration, and tube-forming capacity of endothelial cells in vitro. Mechanistically, through the lncRNA–RNA binding protein–miRNA interaction analysis involving loss of function and gain-of-function experiments, we found that lncRNA PNKY inhibited the binding of miR124 to PTBP1 and maintained the homeostasis of choroidal vascular function by promoting Bcl-2 like protein 11 (BIM), and its dysfunction led to exacerbation of CNV lesion. Therefore, this study suggests that the lncPNKY/PTBP1–miR-124 axis is involved in regulating the development of CNV, providing a potential therapeutic target for the treatment of CNV.
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影响因子：
16.6
作者：
Huang X;Zhou G;Wu W;Duan Y;Ma G;Song J;Xiao R;Vandenberghe L;Zhang F;D'Amore PA;Lei H
通讯作者：
Lei H
影响因子：
8
作者：
Peng WX;Koirala P;Mo YY
通讯作者：
Mo YY
影响因子：
5.3
作者：
Salehi S;Taheri MN;Azarpira N;Zare A;Behzad-Behbahani A
通讯作者：
Behzad-Behbahani A
影响因子：
3.9
作者：
Sawicka, Kirsty;Bushell, Martin;Willis, Anne E.
通讯作者：
Willis, Anne E.
DOI：
10.1136/bjophthalmol-2014-305702
发表时间：
2014-09
期刊：
The British journal of ophthalmology
影响因子：
--
作者：
Schmidt-Erfurth U;Chong V;Loewenstein A;Larsen M;Souied E;Schlingemann R;Eldem B;Monés J;Richard G;Bandello F;European Society of Retina Specialists
通讯作者：
European Society of Retina Specialists