Li Xiu-Miao, Ge Hui-Min, Yao Jin, Zhou Yun-Fan, Yao Mu-Di, Liu Chang, Hu Hai-Tao, Zhu Yun-Xi, Shan Kun, Yan Biao, Jiang Qin
The Affiliated Eye Hospital of Nanjing Medical University, Nanjing, China.
The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, China.
Cell Physiol Biochem. 2018;47(4):1630-1642. doi: 10.1159/000490982. Epub 2018 Jun 27.
BACKGROUND/AIMS: Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown.
Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function.
Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro.
This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.
背景/目的:翼状胬肉是一种常见的眼表疾病,病因不明,当其侵入角膜时会威胁视力。环状RNA(circRNA)是一类新型的RNA转录本,参与多种生理和病理过程。然而,circRNA在翼状胬肉发病机制中的作用仍 largely未知。
进行全基因组circRNA表达谱分析以鉴定与翼状胬肉相关的circRNA。进行基因本体(GO)分析、通路分析和微小RNA(miRNA)反应元件分析,以预测翼状胬肉中差异表达circRNA的功能。进行MTT法、Ki67染色、Transwell实验、Hoechst 33342染色和钙黄绿素-AM/碘化丙啶(PI)染色,以确定circRNA沉默对翼状胬肉成纤维细胞和上皮细胞功能的影响。
在翼状胬肉组织中鉴定出约669种circRNA异常表达。GO分析表明,差异表达circRNA的宿主基因靶向细胞外基质组织(本体:生物学过程)、细胞质(本体:细胞成分)和蛋白质结合(本体:分子功能)。通路分析显示,失调的circRNA介导的调控网络大多富集于粘着斑信号通路。值得注意的是,circ_0085020(circ-LAPTM4B)被证明是翼状胬肉的潜在生物标志物。circ_008…此处原文有误,正确为circ_0085020(circ-LAPTM4B)沉默在体外影响翼状胬肉成纤维细胞和上皮细胞的活力、增殖、迁移和凋亡。
本研究提供了证据表明circRNA参与翼状胬肉的发病机制,可能构成翼状胬肉治疗干预的有前景的靶点。