通过微阵列综合分析鉴定 2 型糖尿病中潜在的功能性 circRNA-miRNA-mRNA 调控网络。

IF 2.5 Q3 ENDOCRINOLOGY & METABOLISM Minerva endocrinology Pub Date : 2024-03-01 Epub Date: 2021-04-01 DOI:10.23736/S2724-6507.21.03370-8
Zijing Li, Xiaowen Deng, Yuqing Lan
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引用次数: 0

摘要

目的:环状 RNA(circRNA)通过吸附微 RNA(miRNA)发挥 miRNA 海绵的功能,从而调节信使 RNA(mRNA)的表达。与2型糖尿病(T2DM)相关的circRNA-miRNA-mRNA调控网络还很少被探索。建立与 T2DM 相关的 circRNA-miRNA-mRNA 调控网络有助于加深我们对 T2DM 分子机制和治疗靶点的理解:差异表达的circRNAs(DEcircRNAs)、miRNAs(DEmiRNAs)和mRNAs(DEmRNAs)分别来自基因表达总库(GEO)微阵列数据集GSE114248、GSE51674和GSE95849。构建了与 T2DM 相关的 circRNAmiRNA-mRNA 调控网络及其子网络。利用蛋白质-蛋白质相互作用(PPI)网络筛选了枢纽基因。最后,构建了枢纽基因相关网络。进行了基因本体(GO)分析和京都基因组百科全书(KEGG)通路分析:结果:circRNA-miRNA-mRNA网络包括9个circRNA、24个miRNA和320个mRNA。当选择 4 个关键 circRNA(circMYO9B、circGRAMD1B、circTHAP4 和 circTMC7)时,子网络包括 4 个 circRNA、18 个 miRNA 和 307 个 mRNA。随后,从 PPI 网络中提取了 8 个中心基因(SIRT1、GNG7、KDR、FOS、SIN3B、STAT1、SP1 和 MAPK3)。GO和KEGG通路分析表明,该网络可能参与氧化应激反应、炎症调控、新生血管生成、内分泌和癌症相关过程等:结论:构建了一个circRNA-miRNA-枢纽基因调控网络,并分析了枢纽基因的潜在功能。四个重要的circRNA(circMYO9B、circGRAMD1B、circTHAP4和circTMC7)可能参与了T2DM的发生和发展,这一发现为T2DM及其并发症的分子机制和治疗靶点提供了新的视角。未来的研究需要验证这4种circRNA的海绵效应和机制。
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Identification of a potentially functional circRNA-miRNA-mRNA regulatory network in type 2 diabetes mellitus by integrated microarray analysis.

Background: Circular RNAs (circRNAs) function as miRNA sponges by adsorbing microRNAs (miRNAs), thereby regulating messenger RNA (mRNA) expression. The circRNA-miRNA-mRNA regulatory network associated with type 2 diabetes mellitus (T2DM) has rarely been explored. A circRNA-miRNA-mRNA regulatory network associated with T2DM was established to help deepen our understanding of the molecular mechanism of and therapeutic targets for T2DM.

Methods: Differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) were derived from the Gene Expression Omnibus (GEO) microarray datasets GSE114248, GSE51674 and GSE95849, respectively. A circRNA-miRNA-mRNA regulatory network associated with T2DM and its subnetwork were constructed. The hub genes were screened using a protein-protein interaction (PPI) network. Finally, a hub gene-related network was constructed. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed.

Results: The circRNA-miRNA-mRNA network included 9 circRNAs, 24 miRNAs and 320 mRNAs. When four key circRNAs (circMYO9B, circGRAMD1B, circTHAP4 and circTMC7) were chosen, the subnetwork contained 4 circRNAs, 18 miRNAs and 307 mRNAs. Afterwards, 8 hub genes (SIRT1, GNG7, KDR, FOS, SIN3B, STAT1, SP1, and MAPK3) were extracted from the PPI network. GO and KEGG pathway analyses revealed that the network might be involved in oxidative stress responses, regulation of inflammation, neovascularization, endocrine and cancer-related processes, etc.

Conclusions: A circRNA-miRNA-hub gene regulatory network was constructed, and the potential functions of the hub genes were analyzed. Four important circRNAs (circMYO9B, circGRAMD1B, circTHAP4 and circTMC7) might be involved in the occurrence and development of T2DM, and this finding provides new insight into the molecular mechanism of and therapeutic targets for T2DM and its complications. Future studies are needed to validate the sponge effects and mechanisms of these 4 circRNAs.

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