LINC00167 Regulates RPE Differentiation by Targeting the miR-203a-3p/SOCS3 Axis

Xue Chen; Ruxu Sun; Daidi Yang; Chao Jiang; Qinghuai Liu

doi:10.1016/j.omtn.2019.12.040

LINC00167 Regulates RPE Differentiation by Targeting the miR-203a-3p/SOCS3 Axis

Mol Ther Nucleic Acids. 2020 Mar 6:19:1015-1026. doi: 10.1016/j.omtn.2019.12.040. Epub 2020 Jan 15.

Authors

Xue Chen¹, Ruxu Sun¹, Daidi Yang¹, Chao Jiang¹, Qinghuai Liu²

Affiliations

¹ Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210029, China.
² Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing 210029, China. Electronic address: liuqh@njmu.edu.cn.

Abstract

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) play significant roles in various diseases; however, their roles in age-related macular degeneration (AMD) remain unclear. Dedifferentiation and dysfunction of retinal pigment epithelium (RPE) cells have been shown to contribute to AMD etiology in several studies. Herein, we found that lncRNA LINC00167 was downregulated in RPE-choroid samples of AMD patients and dysfunctional RPE cells, and it was consistently upregulated along with RPE differentiation. In vitro study indicated that reduced endogenous LINC00167 expression resulted in RPE dedifferentiation, which was typified by attenuated expression of RPE markers, reduced vascular endothelial growth factor A secretion, accumulation of mitochondrial reactive oxygen species, and interrupted phagocytic ability. Mechanistically, LINC00167 functioned as a sponge for microRNA miR-203a-3p to restore the expression of the suppressor of cytokine signaling 3 (SOCS3), which further inhibited the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway. Taken together, our study demonstrated that LINC00167 showed a protective role in AMD by maintaining RPE differentiation through the LINC00167/miR-203a-3p/SOCS3 axis and might be a potential therapeutic target for AMD.

Keywords: LINC00167; SOCS3; age-related macular degeneration; miR-203a-3p; retinal pigment epithelium.