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克罗恩病患者结肠组织中环状 RNA 的表达变化。

Circular RNA expression alterations in colon tissues of Crohn's disease patients.

机构信息

Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Inflammatory Bowel Disease Research Centre, Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, P.R. China.

出版信息

Mol Med Rep. 2019 May;19(5):4500-4506. doi: 10.3892/mmr.2019.10070. Epub 2019 Mar 21.

Abstract

Genetic factors are crucial in the development of Crohn's disease (CD). Circular RNAs (circRNAs) are known to function as microRNA (miRNA) sponges and regulate a number of signalling pathways via circRNA‑miRNA interactions. As competing endogenous RNAs, the functions of circRNAs in CD should be investigated. In the present study, colon biopsy tissues were collected from ileocolon (L3)‑active CD patients and healthy controls. circRNA microarrays were performed with colon tissues from 3 CD patients and 3 controls. Subsequently, the candidate circRNAs were verified via reverse transcription‑quantitative polymerase chain reaction using colon tissues from a further 10 CD patients and 10 controls. Targeted miRNAs, genes and pathways of candidate circRNAs were predicted and analysed. Arraystar circRNA microarrays demonstrated that there were 163 upregulated circRNAs targeting 435 miRNAs and 55 downregulated circRNAs targeting 207 miRNAs (fold‑change >2 and P<0.01) in CD patients. As a candidate circRNA, hsa‑circRNA‑102685 was observed to putatively target hsa‑miR‑146b‑5p, hsa‑miR‑182‑5p and hsa‑miR‑146a‑5p. Furthermore, Kyoto Encyclopaedia of Genes and Genomes pathway analysis predicted that hsa‑circRNA‑102685 potentially participated in apoptosis, and in the Toll‑like receptor and p53 signalling pathways. Overall, the current study suggested that circRNA alterations serve an important role in the pathogenesis of CD. circRNAs, such as hsa‑circRNA‑102685, are involved in certain important signalling pathways of CD, and may be novel targets for diagnosis or treatment in this disease.

摘要

遗传因素在克罗恩病 (CD) 的发生发展中起着至关重要的作用。已知环状 RNA (circRNA) 可作为 microRNA (miRNA) 海绵,通过 circRNA-miRNA 相互作用调节许多信号通路。作为竞争性内源性 RNA,circRNA 在 CD 中的功能需要进一步研究。本研究收集了活动期回肠末端 CD 患者和健康对照者的结肠活检组织。使用 3 例 CD 患者和 3 例对照者的结肠组织进行 circRNA 微阵列分析。随后,使用另外 10 例 CD 患者和 10 例对照者的结肠组织,通过逆转录-定量聚合酶链反应进一步验证候选 circRNA。预测和分析候选 circRNA 的靶向 miRNA、基因和通路。Arraystar circRNA 微阵列显示,CD 患者中存在 163 个上调的 circRNA,靶向 435 个 miRNA,以及 55 个下调的 circRNA,靶向 207 个 miRNA(fold-change>2,P<0.01)。作为候选 circRNA,hsa-circRNA-102685 被观察到可能靶向 hsa-miR-146b-5p、hsa-miR-182-5p 和 hsa-miR-146a-5p。此外,京都基因与基因组百科全书通路分析预测 hsa-circRNA-102685 可能参与细胞凋亡以及 Toll 样受体和 p53 信号通路。总的来说,本研究表明 circRNA 改变在 CD 的发病机制中起重要作用。circRNA,如 hsa-circRNA-102685,参与 CD 的某些重要信号通路,可能成为该疾病诊断或治疗的新靶点。

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