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鉴定并初步分析可能与人类椎间盘退变相关的 circRNAs。

Confirmation and preliminary analysis of circRNAs potentially involved in human intervertebral disc degeneration.

机构信息

Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.

出版信息

Mol Med Rep. 2017 Dec;16(6):9173-9180. doi: 10.3892/mmr.2017.7718. Epub 2017 Oct 4.

DOI:10.3892/mmr.2017.7718
PMID:28990083
Abstract

Circular RNAs (circRNAs) are relatively recently identified noncoding RNAs that are ubiquitously expressed in human tissues and serve key functions in regulating gene expression. However, few studies have focused on human intervertebral disc degeneration (IDD) circRNAs, and the potential role of circRNAs in IDD has not been described in detail. In the present study, circRNA expression data was downloaded from the Gene Expression Omnibus database, and circRNAs in the human intervertebral disc were classified according to their length, indicating their uniform distribution of circRNAs of different lengths. Gene Ontology analysis was performed, which indicated that the differentially expressed circRNAs were mainly produced as a result of catalytic activity and from binding genes in the molecular function category, cell part genes in the cellular component category, and cellular and metabolic process genes in the biological process category. Classification analysis divided the circRNAs host genes into 16 classes; with nucleic acid binding genes ranked as the most common host gene type in IDD tissue. Pathway analysis indicated that >15 signaling pathways may serve different roles in IDD, and Wnt signaling, gonadotropin‑releasing hormone receptor and integrin signaling pathways may serve important roles. Using co‑expression analysis, 76 differentially expressed circRNAs and host gene pairs were identified, which were divided into four groups: CircRNAs and their host genes downregulated; circRNAs downregulated and host genes upregulated; circRNAs and their host genes upregulated; and circRNAs upregulated and host genes downregulated. Finally, hsa_circ_0008305 upregulation and hsa_circ_0041946 downregulation were validated in IDD using reverse transcription‑quantitative polymerase chain reaction. In conclusion, the findings of the present study may shed light on the potential roles of circRNAs in IDD and the possibility for their use in the diagnosis and clinical treatment of IDD in the future.

摘要

环状 RNA(circRNA)是相对较新发现的非编码 RNA,广泛存在于人体组织中,在调节基因表达方面发挥着关键作用。然而,目前关于人类椎间盘退变(IDD)circRNA 的研究较少,circRNA 在 IDD 中的潜在作用尚未详细描述。本研究从基因表达综合数据库中下载了 circRNA 表达数据,并根据长度对人类椎间盘的 circRNA 进行了分类,表明不同长度的 circRNA 分布均匀。GO 分析表明,差异表达的 circRNA 主要由催化活性产生,从分子功能类别中的结合基因、细胞成分类别中的细胞部分基因和生物过程类别中的细胞和代谢过程基因产生。分类分析将 circRNA 宿主基因分为 16 类;在 IDD 组织中,核酸结合基因是最常见的宿主基因类型。通路分析表明,超过 15 种信号通路可能在 IDD 中发挥不同的作用,Wnt 信号通路、促性腺激素释放激素受体和整合素信号通路可能发挥重要作用。通过共表达分析,鉴定出 76 个差异表达的 circRNA 和宿主基因对,它们分为四组:circRNA 和其宿主基因下调;circRNA 下调和宿主基因上调;circRNA 和其宿主基因上调;circRNA 上调和宿主基因下调。最后,通过逆转录-定量聚合酶链反应在 IDD 中验证了 hsa_circ_0008305 的上调和 hsa_circ_0041946 的下调。综上所述,本研究的结果可能为 circRNA 在 IDD 中的潜在作用及其在未来 IDD 的诊断和临床治疗中的应用提供线索。

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