Traditional Chinese Medicine School, Beijing University of Chinese Medicine, Beijing 100029, China.
Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK.
Int J Mol Sci. 2023 Jun 19;24(12):10323. doi: 10.3390/ijms241210323.
MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play critical roles in the regulation of different biological processes, but their underlying mechanisms in diabetes mellitus (DM) are still largely unknown. This study aimed to gain a better understanding of the functions of miRNAs and tsRNAs in the pathogenesis of DM. A high-fat diet (HFD) and streptozocin (STZ)-induced DM rat model was established. Pancreatic tissues were obtained for subsequent studies. The miRNA and tsRNA expression profiles in the DM and control groups were obtained by RNA sequencing and validated with quantitative reverse transcription-PCR (qRT-PCR). Subsequently, bioinformatics methods were used to predict target genes and the biological functions of differentially expressed miRNAs and tsRNAs. We identified 17 miRNAs and 28 tsRNAs that were significantly differentiated between the DM and control group. Subsequently, target genes were predicted for these altered miRNAs and tsRNAs, including Nalcn, Lpin2 and E2f3. These target genes were significantly enriched in localization as well as intracellular and protein binding. In addition, the results of KEGG analysis showed that the target genes were significantly enriched in the Wnt signaling pathway, insulin pathway, MAPK signaling pathway and Hippo signaling pathway. This study revealed the expression profiles of miRNAs and tsRNAs in the pancreas of a DM rat model using small RNA-Seq and predicted the target genes and associated pathways using bioinformatics analysis. Our findings provide a novel aspect in understanding the mechanisms of DM and identify potential targets for the diagnosis and treatment of DM.
微小 RNA（miRNA）和转移 RNA 衍生的小 RNA（tsRNA）在调节不同的生物过程中发挥着关键作用，但它们在糖尿病（DM）中的潜在机制在很大程度上仍然未知。本研究旨在更好地了解 miRNA 和 tsRNA 在 DM 发病机制中的作用。建立了高脂肪饮食（HFD）和链脲佐菌素（STZ）诱导的 DM 大鼠模型。获得胰腺组织进行后续研究。通过 RNA 测序获得 DM 和对照组的 miRNA 和 tsRNA 表达谱，并通过定量逆转录-PCR（qRT-PCR）进行验证。随后，使用生物信息学方法预测差异表达的 miRNA 和 tsRNA 的靶基因和生物学功能。我们鉴定了 17 个 miRNA 和 28 个 tsRNA，它们在 DM 和对照组之间存在显著差异。随后，为这些改变的 miRNA 和 tsRNA 预测了靶基因，包括 Nalcn、Lpin2 和 E2f3。这些靶基因在定位以及细胞内和蛋白质结合方面显著富集。此外，KEGG 分析的结果表明，靶基因在 Wnt 信号通路、胰岛素通路、MAPK 信号通路和 Hippo 信号通路中显著富集。本研究使用小 RNA-Seq 揭示了 DM 大鼠模型胰腺中 miRNA 和 tsRNA 的表达谱，并通过生物信息学分析预测了靶基因和相关通路。我们的研究结果为理解 DM 的机制提供了一个新的方面，并为 DM 的诊断和治疗确定了潜在的靶点。
