Metformin, a widely used anti-diabetic drug, has demonstrated its efficacy in addressing various inflammatory conditions. tRNA-derived small RNA (tsRNA), a novel type of small non-coding RNA, exhibits diverse regulatory functions and holds promise as both a diagnostic biomarker and a therapeutic target for various diseases. The purpose of this study is to investigate whether the abundance of tsRNAs changed in LPS versus LPS + metformin-treated cells, utilizing microarray technology. Firstly, we established an in vitro lipopolysaccharide (LPS)-induced inflammation model using RAW264.7 macrophages and assessed the protective effects of metformin against inflammatory damage. Subsequently, we extracted total RNA from both LPS-treated and metformin + LPS-treated cell samples for microarray analysis to identify differentially abundant tsRNAs (DA-tsRNAs). Furthermore, we conducted bioinformatics analysis to predict target genes for validated DA-tsRNAs and explore the biological functions and signaling pathways associated with DA-tsRNAs. Notably, metformin was found to inhibit the inflammatory response in RAW264.7 macrophages. The microarray results revealed a total of 247 DA-tsRNAs, with 58 upregulated and 189 downregulated tsRNAs in the Met + LPS group compared to the LPS group. The tsRNA-mRNA network was visualized, shedding light on potential interactions. The results of bioinformatics analysis suggested that these potential targets of specific tsRNAs were mainly related to inflammation and immunity. Our study provides compelling evidence that metformin exerts anti-inflammatory effects and modulates the abundance of tsRNAs in LPS-treated RAW264.7 macrophages. These findings establish a valuable foundation for using tsRNAs as potential biomarkers for metformin in the treatment of inflammatory conditions.

中文翻译：

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用二甲双胍处理的 LPS 攻击的巨噬细胞中 tRNA 衍生的小 RNA (tsRNA) 的微阵列分析

二甲双胍是一种广泛使用的抗糖尿病药物，已证明其在解决各种炎症方面的功效。 tRNA 衍生的小 RNA (tsRNA) 是一种新型的小非编码 RNA，具有多种调节功能，有望作为多种疾病的诊断生物标志物和治疗靶点。本研究的目的是利用微阵列技术研究 LPS 与 LPS + 二甲双胍处理的细胞中 tsRNA 的丰度是否发生变化。首先，我们利用RAW264.7巨噬细胞建立了体外脂多糖（LPS）诱导的炎症模型，并评估了二甲双胍对炎症损伤的保护作用。随后，我们从 LPS 处理和二甲双胍 + LPS 处理的细胞样本中提取总 RNA 进行微阵列分析，以鉴定差异丰富的 tsRNA (DA-tsRNA)。此外，我们进行了生物信息学分析来预测经过验证的 DA-tsRNA 的靶基因，并探索与 DA-tsRNA 相关的生物学功能和信号通路。值得注意的是，二甲双胍被发现可以抑制 RAW264.7 巨噬细胞的炎症反应。微阵列结果显示，与 LPS 组相比，Met + LPS 组总共有 247 个 DA-tsRNA，其中 58 个上调，189 个下调 tsRNA。 tsRNA-mRNA 网络被可视化，揭示了潜在的相互作用。生物信息学分析结果表明，这些特定tsRNA的潜在靶点主要与炎症和免疫相关。我们的研究提供了令人信服的证据，表明二甲双胍发挥抗炎作用并调节 LPS 处理的 RAW264.7 巨噬细胞中 tsRNA 的丰度。这些发现为使用 tsRNA 作为二甲双胍治疗炎症的潜在生物标志物奠定了宝贵的基础。