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长链非编码 RNA ZNF503-AS1 通过下调 ZNF503 表达促进 RPE 分化。

LncRNA ZNF503-AS1 promotes RPE differentiation by downregulating ZNF503 expression.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, State Key Laboratory of Reproductive Medicine, Nanjing 210029, China.

Department of Ophthalmology and Vision Science, Eye &ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200023, China.

出版信息

Cell Death Dis. 2017 Sep 7;8(9):e3046. doi: 10.1038/cddis.2017.382.

DOI:10.1038/cddis.2017.382
PMID:28880276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5636965/
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.

摘要

长链非编码 RNA（lncRNA）在各种生物过程中发挥着重要作用。我们之前的工作揭示了视网膜色素上皮（RPE）细胞的去分化有助于年龄相关性黄斑变性（AMD）的发病机制。在此，我们研究了 lncRNA 在 RPE 分化中的作用。我们使用微阵列鉴定了人诱导多能干细胞（hiPSC）和 hiPSC 衍生的 RPE 细胞中的 lncRNA 表达谱。总共鉴定出 217 个随着分化而差异表达的 lncRNA，其中 13 个 lncRNA 的倍数变化超过 2。lncRNA ZNF503-AS1 位于 RPE 细胞的细胞质中，随着 RPE 分化持续上调，在 AMD 患者的 RPE-脉络膜中下调。体外研究进一步表明，ZNF503-AS1 不足可抑制 RPE 分化，并促进其增殖和迁移。由于 ZNF503-AS1 是从 ZNF503 基因座的反义链转录而来的，我们进一步揭示了其对 ZNF503 表达的调节作用。ZNF503-AS1 与 ZNF503 的表达呈负相关。我们的结果还表明，ZNF503 可抑制 RPE 分化，并促进其增殖和迁移。因此，ZNF503-AS1 通过下调 ZNF503 的表达，可能促进 RPE 分化。此外，核因子-κB 被认为是 ZNF503-AS1 的潜在上游转录因子，通过调节 ZNF503-AS1 的表达参与促进 RPE 分化。综上所述，我们的研究确定了一组与 RPE 分化相关的 lncRNA，以及 ZNF503-AS1 在萎缩性 AMD 发病机制中的潜在作用，这可能有助于 AMD 患者的干预。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/223fa2ff8c6c/cddis2017382f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/43eccac800e6/cddis2017382f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/5eda9bdb9475/cddis2017382f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/e83847807ea4/cddis2017382f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/40b4fc78de06/cddis2017382f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/4ab77b92831b/cddis2017382f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/0da65e81b945/cddis2017382f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/223fa2ff8c6c/cddis2017382f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/43eccac800e6/cddis2017382f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/5eda9bdb9475/cddis2017382f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/e83847807ea4/cddis2017382f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/40b4fc78de06/cddis2017382f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/4ab77b92831b/cddis2017382f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/0da65e81b945/cddis2017382f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/358d/5636965/223fa2ff8c6c/cddis2017382f7.jpg

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