Department of Ophthalmology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Provincial Clinical Research Center of Diabetes Mellitus and its Chronic Complications, Guangzhou, China.
Minerva Endocrinol (Torino). 2024 Mar;49(1):33-46. doi: 10.23736/S2724-6507.21.03370-8. Epub 2021 Apr 1.
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.
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.
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.
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.
环状 RNA（circRNAs）通过吸附 microRNA（miRNA）作为 miRNA 海绵，从而调节信使 RNA（mRNA）的表达。与 2 型糖尿病（T2DM）相关的 circRNA-miRNA-mRNA 调控网络很少被探索。建立一个与 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。
从基因表达综合数据库（GEO）微阵列数据集 GSE114248、GSE51674 和 GSE95849 中分别提取差异表达的 circRNAs（DEcircRNAs）、miRNAs（DEmiRNAs）和 mRNAs（DEmRNAs）。构建与 T2DM 相关的 circRNA-miRNA-mRNA 调控网络及其子网络。使用蛋白质-蛋白质相互作用（PPI）网络筛选枢纽基因。最后，构建一个枢纽基因相关的网络。进行基因本体（GO）分析和京都基因与基因组百科全书（KEGG）通路分析。
circRNA-miRNA-mRNA 网络包含 9 个 circRNAs、24 个 miRNAs 和 320 个 mRNAs。当选择四个关键 circRNAs（circMYO9B、circGRAMD1B、circTHAP4 和 circTMC7）时，子网络包含 4 个 circRNAs、18 个 miRNAs 和 307 个 mRNAs。随后，从 PPI 网络中提取了 8 个枢纽基因（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、炎症调节、新生血管生成、内分泌和癌症相关过程等。
构建了 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 circRNAs（circMYO9B、circGRAMD1B、circTHAP4 和 circTMC7）可能参与 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见解。未来需要进一步验证这四个 circRNAs 的海绵作用和机制。
