Long Non-Coding RNA PNKY Modulates the Development of Choroidal Neovascularization

Lianjun Shi; Xue Han; Chang Liu; Xiumiao Li; Shuting Lu; Qin Jiang; Jin Yao

doi:10.3389/fcell.2022.836031

Long Non-Coding RNA PNKY Modulates the Development of Choroidal Neovascularization

Front Cell Dev Biol. 2022 Feb 21:10:836031. doi: 10.3389/fcell.2022.836031. eCollection 2022.

Authors

Lianjun Shi^{1

2}, Xue Han^{1

2}, Chang Liu^{3

4

5}, Xiumiao Li^{1

2}, Shuting Lu^{1

2}, Qin Jiang^{1

2}, Jin Yao^{1

2}

Affiliations

¹ The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.
² The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
³ Eye Institute, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
⁴ NHC Key Laboratory of Myopia Fudan University, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, China.
⁵ Shanghai Key Laboratory of Visual Impairment and Restoration, Fudan University, Shanghai, China.

Abstract

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.

Keywords: PNKY; choroidal neovascularization; long non-coding RNA; miRNA; polypyrimidine bundle binding protein 1.