LncRNA ZNF503-AS1 promotes RPE differentiation by downregulating ZNF503 expression

被引：42

作者：

Chen, Xue ^{[1
,2
,3
,4
]}

Jiang, Chao ^{[1
]}

Qin, Bing ^{[1
,5
]}

Liu, Guohua ^{[6
]}

Ji, Jiangdong ^{[1
]}

Sun, Xiantao ^{[7
]}

Xu, Min ^{[8
]}

Ding, Sijia ^{[1
]}

Zhu, Meidong ^{[9
]}

Huang, Guofu ^{[10
]}

Yan, Biao ^{[11
]}

Zhao, Chen ^{[1
,2
,3
,4
,7
]}

机构：

[1] Nanjing Med Univ, State Key Lab Reprod Med, Affiliated Hosp 1, Dept Ophthalmol, Nanjing 210029, Jiangsu, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Ophthalmol & Vis Sci, Shanghai 200023, Peoples R China

[3] Fudan Univ, Key Lab Myopia, State Hlth Minist, Shanghai 200023, Peoples R China

[4] Shanghai Key Lab Visual Impairment & Restorat, Shanghai 200023, Peoples R China

[5] First Peoples Hosp Suqian, Dept Ophthalmol, Suqian 223800, Peoples R China

[6] Shandong Univ, Qilu Childrens Hosp, Dept Ophthalmol, Jinan 250000, Shandong, Peoples R China

[7] Childrens Hosp Zhengzhou, Dept Ophthalmol, Zhengzhou 450053, Henan, Peoples R China

[8] Northern Jiangsu Peoples Hosp, Dept Ophthalmol, Yangzhou 225000, Jiangsu, Peoples R China

[9] Univ Sydney, Save Sight Inst, Discipline Clin Ophthalmol & Eye Hlth, Sydney, NSW 2000, Australia

[10] Nanchang Univ, Affiliated Hosp 3, Dept Ophthalmol, Nanchang 330000, Jiangxi, Peoples R China

[11] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Res Ctr, Shanghai 200023, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

LONG NONCODING RNAS; RETINAL-PIGMENT EPITHELIUM; DOMINANT RETINITIS-PIGMENTOSA; MACULAR DEGENERATION; CELLS; IDENTIFICATION; DEDIFFERENTIATION; PROLIFERATION; RETINOPATHY; MECHANISMS;

D O I：

10.1038/cddis.2017.382

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-kappa B 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.

引用

页码：e3046 / e3046

页数：11

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