Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease
Genome-Wide Identification of Circular RNAs as a Novel Class of Putative Biomarkers for an Ocular Surface Disease
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环状 RNA 的全基因组鉴定作为眼表疾病的新型假定生物标志物
DOI：
10.1159/000490982
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发表时间：
2018-01-01
影响因子：
--
通讯作者：
Jiang, Qin
中科院分区：
文献类型：
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作者：
Li, Xiu-Miao;Ge, Hui-Min;Jiang, Qin
背景/目的：翼状胬肉是一种常见的眼表疾病，病因不明，当它侵入角膜时会威胁视力。环状RNA（CircRNA）是一类参与多种生理和病理过程的新型RNA转录物。然而，circRNA在翼状胬肉发病机制中的作用仍然很大程度上未知。方法：进行全基因组circRNA表达谱分析以鉴定翼状胬肉相关的circRNA。通过GO分析、通路分析和miRNA反应元件分析来预测翼状胬肉中差异表达的circRNA的功能。采用MTT法、Ki 67染色法、Transwell法、Hoechst 33342染色法和Calcein-AM/PI染色法检测circRNA沉默对翼状胬肉成纤维细胞和上皮细胞功能的影响。结果：翼状胬肉组织中约有669条circRNA表达异常。GO分析表明，差异表达的circRNA的宿主基因靶向细胞外基质组织（本体：生物过程），细胞质（本体：细胞组分）和蛋白质结合（本体：分子功能）。通路分析表明，调控失调的circRNA介导的调控网络主要集中在粘着斑信号通路。值得注意的是，circ_0085020（circ-LAPTM 4 B）被显示为翼状胬肉的潜在生物标志物。circ_0085020（circ-LAPTM 4 B）沉默影响体外翼状胬肉成纤维细胞和上皮细胞的活力、增殖、迁移和凋亡。结论：这项研究提供了证据表明，circRNA参与翼状胬肉的发病机制，并可能成为翼状胬肉治疗干预的有希望的靶点。
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. Methods: 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. Results: 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. Conclusions: This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.