Identification of Potentially Functional Circular RNA/Long Noncoding RNA-MicroRNA-mRNA Regulatory Networks Associated with Vascular Injury in Type 2 Diabetes Mellitus by Integrated Microarray Analysis.
Identification of Potentially Functional Circular RNA/Long Noncoding RNA-MicroRNA-mRNA Regulatory Networks Associated with Vascular Injury in Type 2 Diabetes Mellitus by Integrated Microarray Analysis.
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DOI：
10.1155/2023/3720602
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发表时间：
2023
影响因子：
4.3
通讯作者：
Cai, Ying
中科院分区：
文献类型：
--
作者：
Leng, Yi;Wang, Ming-zhu;Xie, Kang-ling;Cai, Ying
本研究旨在阐明2型糖尿病（T2 DM）血管损伤相关的潜在环状RNA（circRNA）/长链非编码RNA-（lncRNA-）microRNA-（miRNA-）mRNA调控网络。从T2 DM相关表达数据集中筛选差异表达基因（DEG），将其与T2 DM血管损伤相关基因进行融合，获得候选DEG，构建DEG相互作用网络。利用miRWalk、mirDIP和DIANA TOOLS数据库预测候选基因的上游miRNAs，利用DIANA-LncBase/circBank数据库预测miRNAs的上游lncRNA/circRNA，构建circRNA/lncRNA-miRNA-mRNA调控网络。采集2型糖尿病合并大血管病变患者外周血，对关键因子的表达及相关性进行临床验证。差异分析筛选出37个与2型糖尿病血管损伤相关的候选DEG。MAPK 3是与T2 DM血管损伤相关的核心基因。在预测的MAPK 3的上游miRNAs中，根据结合分数，miR-4270、miR-92 a-2- 5 p、miR-423- 5 p和miR-613排名最高。进一步预测了4种miRNAs的上游lncRNA和circRNA，得到11种候选lncRNA和3种候选circRNA。此外，在伴有大血管病变的T2 DM患者外周血中，KCNQ 1 OT 1、circ_0020316和MAPK 3上调，而miR-92 a-2- 5 p下调。在机制上，KCNQ 1 OT 1和circ_0020316与反向靶向MAPK 3的miR-92 a-2- 5 p结合。总体而言，KCNQ 1 OT 1/circ_0020316-miR-92 a-2- 5 p-MAPK 3共表达调控网络可能促进T2 DM的血管损伤。
This research is aimed at figuring out the potential circular RNA (circRNA)/long noncoding RNA- (lncRNA-) microRNA- (miRNA-) mRNA regulatory networks associated with a vascular injury in type 2 diabetes mellitus (T2DM). Differentially expressed genes (DEGs) screened in T2DM-related expression datasets were intersected with genes associated with vascular injury in T2DM to obtain candidate DEGs, followed by the construction of an interaction network of DEGs. The upstream miRNAs of candidate genes were predicted by mirDIP, miRWalk, and DIANA TOOLS databases, and the upstream lncRNAs/circRNAs of miRNAs by DIANA-LncBase/circBank database, followed by the construction of circRNA/lncRNA-miRNA-mRNA regulatory networks. Peripheral blood was attained from T2DM patients with macroangiopathy for clinical validation of expression and correlation of key factors. Differential analysis screened 37 candidate DEGs correlated with vascular injury in T2DM. Besides, MAPK3 was a core gene associated with vascular injury in T2DM. Among the predicted upstream miRNAs of MAPK3, miR-4270, miR-92a-2-5p, miR-423-5p, and miR-613 ranked at the top according to binding scores. The upstream lncRNAs and circRNAs of the 4 miRNAs were further predicted, obtaining 11 candidate lncRNAs and 3 candidate circRNAs. Moreover, KCNQ1OT1, circ_0020316, and MAPK3 were upregulated, but miR-92a-2-5p was downregulated in the peripheral blood of T2DM patients with macroangiopathy. Mechanistically, KCNQ1OT1 and circ_0020316 bound to miR-92a-2-5p that inversely targeted MAPK3. Collectively, KCNQ1OT1/circ_0020316-miR-92a-2-5p-MAPK3 coexpression regulatory networks might promote vascular injury in T2DM.
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