LncRNA ZNF503-AS1 promotes RPE differentiation by downregulating ZNF503 expression

Abstract

Long noncoding RNAs (lncRNAs) have important roles in various biological processes. Our previous work has revealed that dedifferentiation of retinal pigment epithelium (RPE) cells contributes to the pathology of age-related macular degeneration (AMD). Herein, we show roles of lncRNAs in RPE differentiation. We used microarray to identify lncRNA expression profiles in human induced pluripotent stem cells (hiPSCs) and hiPSC-derived RPE cells. A total of 217 differentially expressed lncRNAs along with the differentiation were initially identified, among which 13 lncRNAs showed a consistent fold change of over 2. LncRNA ZNF503-AS1, located in the cytoplasm of RPE cells, was found consistently upregulated along with RPE differentiation, and downregulated in the RPE-choroid of AMD patients. In vitro study further suggested that ZNF503-AS1 insufficiency could inhibit RPE differentiation, and promote its proliferation and migration. As ZNF503-AS1 is transcribed from the antisense strand of the ZNF503 gene locus, we further revealed its regulatory role in ZNF503 expression. ZNF503-AS1 was reversely correlated with ZNF503 expression. Our results also suggested that ZNF503 could inhibit RPE differentiation, and promote its proliferation and migration. Thus, ZNF503-AS1 potentially promotes RPE differentiation through downregulation of ZNF503 expression. In addition, nuclear factor-κB was recognized as a potential upstream transcript factor for ZNF503-AS1, which might participate in promoting RPE differentiation by regulating the expression of ZNF503-AS1. Taken together, our study identifies a group of RPE differentiation relevant lncRNAs, and the potential role of ZNF503-AS1 in the pathology of atrophic AMD, which might help with the intervention of AMD patients.

Altered Long Non-coding RNAs Involved in Immunological Regulation and Associated with Choroidal Neovascularization in Mice

“…Despite several studies reported important roles of particular lncRNAs such as ZNF503-AS1 and BANCR in RPE cells through in vitro studies [22,23], none of them have investigated the role of lncRNAs in CNV. The present study profiled lncRNA and mRNA expression in the mouse model of laser-induced CNV by integrated microarray analysis.…”

“…Among altered lncRNAs in patients with early AMD, RP11-234O6.2 has been demonstrated as having protective effects in the aging RPE model [21]. A few in vitro studies investigated the roles of several certain lncRNAs (such as ZNF503-AS1 and BANCR) in retinal pigment epithelium (RPE) cells [22,23]. Nevertheless, it still remains unclear that the expression profiles, targets, and effects of lncRNAs and their contribution to the pathogenesis of CNV as well as neovascular AMD.…”

Icariin affects cell cycle progression and proliferation of human retinal pigment epithelial cells via enhancing expression of H19

“…LncRNAs arise more attention of ophthalmologists since they contribute to the regulation of RPE cells in various aspects (Kutty et al, 2018;Ye, Li & He, 2017;Chen et al, 2017). To date, several lncRNAs have been identified to play important roles in regulating cellular proliferation and apoptosis in RPE cells (Zhou et al, 2015(Zhou et al, , 2018Li et al, 2018d;Yang et al, 2016), such as lncRNA BDNF-AS, nuclear factor-κB (NF-κB) Interacting LncRNA and Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1).…”

Circular and long non-coding RNAs and their role in ophthalmologic diseases

“…ZNF503-AS1 is regulated by NF-κB which is involved in cellular processes such as inflammation and differentiation of RPE. Targeting both RP-1123406.2 and ZNF503-AS1 is a potential therapeutic strategy for atrophic AMD (Chen et al, 2017a).…”