环状 RNA 表达谱及其在人腹主动脉瘤中的潜在调控作用。
Circular RNA expression profile and its potential regulative role in human abdominal aortic aneurysm.
机构信息
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 180 Fenglin Road, Shanghai, 200032, China.
出版信息
BMC Cardiovasc Disord. 2020 Feb 10;20(1):70. doi: 10.1186/s12872-020-01374-8.
BACKGROUND
This study aimed to identify the differentially expressed circular RNAs (circRNAs) between human abdominal aortic aneurysm (AAA) and the control group.
METHODS
High-throughput sequencing was applied to determine the circRNA expression profiles of 4 paired aortic samples. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was carried out to testify 6 randomly selected dysregulated circRNAs. Kyoto Encyclopedia of Genes and Genomes and Gene ontology (GO) analysis were conducted for functional annotation of the parental genes. Additionally, interaction networks between circRNA and 5 putative microRNA (miRNA) partners were constructed.
RESULTS
Finally, 411 differentially expressed circRNAs were discovered, including 266 downregulated and 145 upregulated circRNAs. Compared with the control group, the expression level of hsa (Homo sapiens) _circ_0005360 (LDLR) and hsa_circ_0002168 (TMEM189) were proved significantly lower in the AAA group by qRT-PCR. Regarding upregulated circRNAs, the most enriched GO molecular function, biological process and cellular component terms were poly(A) RNA binding, negative regulation of transcription from RNA polymerase II promoter and nucleoplasm, respectively. Moreover, circRNA/miRNA interaction networks showed that hsa_circ_0005360/miR-181b and hsa_circ_0002168/miR-15a axis might have a regulative role in human AAA.
CONCLUSIONS
This study revealed new circRNAs potentially related to the pathogenesis of AAA. Further experimental studies are warranted to clarify the potential molecular mechanisms.
背景
本研究旨在鉴定人腹主动脉瘤（AAA）与对照组之间差异表达的环状 RNA（circRNA）。
方法
应用高通量测序技术确定 4 对主动脉样本的 circRNA 表达谱。实时定量逆转录聚合酶链反应（qRT-PCR）验证 6 个随机选择的失调 circRNA。京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析对亲本基因进行功能注释。此外，构建 circRNA 与 5 个假定 microRNA（miRNA）伙伴之间的相互作用网络。
结果
最终发现 411 个差异表达的 circRNA，包括 266 个下调和 145 个上调的 circRNA。与对照组相比，qRT-PCR 证实 hsa（智人）_circ_0005360（LDLR）和 hsa_circ_0002168（TMEM189）在 AAA 组中的表达水平显著降低。对于上调的 circRNA，最富集的 GO 分子功能、生物过程和细胞成分术语分别为 poly（A）RNA 结合、RNA 聚合酶 II 启动子转录的负调控和核质。此外，circRNA/miRNA 相互作用网络表明，hsa_circ_0005360/miR-181b 和 hsa_circ_0002168/miR-15a 轴可能在人类 AAA 中具有调节作用。
结论
本研究揭示了与 AAA 发病机制相关的新的 circRNA。需要进一步的实验研究来阐明潜在的分子机制。
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