Yu Shaobing, Wang Ruxin, Wang Wei
Shanghai Engineering Research Center of Tooth Restoration and Regeneration & Tongji Research Institute of Stomatology & Department of Clinical Laboratory, Stomatological Hospital and Dental School, Tongji University, Shanghai, China.
Department of Endocrinology and Metabolism, The First Affiliated Hospital of Jinan University, Guangzhou Oversea Chinese Hospital, Guangzhou, China.
Heliyon. 2024 May 31;10(11):e32198. doi: 10.1016/j.heliyon.2024.e32198. eCollection 2024 Jun 15.
Periodontitis (PD) has been acknowledged as a complication associated with type 2 diabetes mellitus (T2DM). However, the precise mechanism through which T2DM fosters the development of PD remains elusive. Our objective is to elucidate the connection between these two conditions by conducting bioinformatics analysis.
In this study, we analyzed miRNA datasets pertaining to T2DM and PD sourced from GEO. Through differential expression analysis, we identified common differentially expressed miRNAs (DE-miRNAs) and subsequently analyzed the functional enrichment of these common DE-miRNAs. We further leveraged the PD transcriptome database to select DE-miRNA-targeted mRNAs and examined their association with immune infiltration. Finally, machine learning was used to further screen hub DE-miRNA-targeted mRNAs and validate our data in external datasets.
Two common DE-miRNAs, namely hsa-miR-342-3p and hsa-miR-360, were identified from the miRNA datasets of PD and T2DM. Functional enrichment analysis indicated that these two common DE-miRNAs predominantly participate in Ras, PI3K-Akt, p53, and MAPK signaling pathways. Integration of the PD transcriptome dataset revealed a total of 21 DE-miRNA-targeted mRNAs in PD, with strong correlations observed with plasma cells and dendritic cells. Finally, three hub DE-miRNA-targeted mRNAs (hsa-miR-342-3p-/hsa-miR-360-RASAL2, hsa-miR-360-ENTPD1/PLXDC2) were identified. ENTPD1 exhibited a robust positive correlation with plasma cells and a negative correlation with resting dendritic cells.
Therefore, hsa-miR-342-3p-/hsa-miR-360-RASAL2, as well as hsa-miR-360-ENTPD1/PLXDC2, may serve as diagnostic and therapeutic targets for T2DM-associated PD.
牙周炎(PD)已被公认为是2型糖尿病(T2DM)的一种并发症。然而,T2DM促进PD发展的确切机制仍不清楚。我们的目标是通过生物信息学分析来阐明这两种疾病之间的联系。
在本研究中,我们分析了来自基因表达综合数据库(GEO)的与T2DM和PD相关的miRNA数据集。通过差异表达分析,我们鉴定出常见的差异表达miRNA(DE-miRNA),随后分析了这些常见DE-miRNA的功能富集情况。我们进一步利用PD转录组数据库选择DE-miRNA靶向的mRNA,并研究它们与免疫浸润的关联。最后,使用机器学习进一步筛选枢纽DE-miRNA靶向的mRNA,并在外部数据集中验证我们的数据。
从PD和T2DM的miRNA数据集中鉴定出两种常见的DE-miRNA,即hsa-miR-342-3p和hsa-miR-360。功能富集分析表明,这两种常见的DE-miRNA主要参与Ras、PI3K-Akt、p53和MAPK信号通路。整合PD转录组数据集发现PD中共有21个DE-miRNA靶向的mRNA,与浆细胞和树突状细胞有很强的相关性。最后,鉴定出三个枢纽DE-miRNA靶向的mRNA(hsa-miR-342-3p-/hsa-miR-360-RASAL2、hsa-miR-360-ENTPD1/PLXDC2)。ENTPD1与浆细胞呈强正相关,与静息树突状细胞呈负相关。
因此,hsa-miR-342-3p-/hsa-miR-360-RASAL2以及hsa-miR-360-ENTPD1/PLXDC2可能作为T2DM相关PD的诊断和治疗靶点。