Department of General Surgery, The Eighth People's Hospital of Shanghai, Shanghai 200233, China.
Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China.
Medicina (Kaunas). 2023 Mar 6;59(3):511. doi: 10.3390/medicina59030511.
: To screen key miRNAs and their target genes related to Toll-like receptor (TLR) activation in gastric cancer (GC) cells and analyze them bioinformatically. : Venn diagrams were obtained to screen miRNAs that were upregulated/downregulated in both GSE54129 and GSE164174. The miRTarBase database was used to predict the target genes of upregulated miRNAs. The differentially expressed genes in the regulatory network were analyzed. miR-16-5p expression in different tissue samples and the variations in the methylation states of four hub genes were measured. : We found that GSE54129 included 21 normal gastric tissues and 111 gastric cancer tissues, GSE164174 included 1417 normal gastric tissues and 1423 gastric cancer tissues. Venn diagram analysis results showed that compared with the control group, a total of 68 DEmiRNAs were upregulated in the GSE54129 and GSE164174 datasets, and no common downregulated DEmiRNAs were found. On further analysis of the GSE108345 dataset, we obtained the competing endogenous RNA (ceRNA) network associated with the activation of TLRs, and listed the top 10 lncRNA-miRNA-mRNA networks, including 10 miRNAs, 86 mRNA and 134 lncRNAs. Cytological HuBBA scores yielded a total of 1 miRNA, 16 mRNAs and 45 lncRNAs, of which miR-16-5p scored the highest as it was considered a key miRNA for TLR activation in GC cells, which are important in response against microorganisms. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that endocytosis, microRNAs in cancer and the PI3K-Akt signaling pathway are related to TLR signaling. The results of in vivo experiments indicated that miR-16-5p was highly expressed in gastric cancer cells and tissues. : Hsa-miR-16-5p's target genes mainly play a role by regulating the expression of four genes-MCL1, AP2B1, LAMB1, and RAB11FIP2. The findings provide a scientific basis for the development of immunotherapy for GC.
: 筛选与 Toll 样受体 (TLR) 激活相关的关键 miRNA 及其靶基因，并进行生物信息学分析。 : 使用 Venn 图筛选在 GSE54129 和 GSE164174 中均上调/下调的 miRNA。使用 miRTarBase 数据库预测上调 miRNA 的靶基因。分析调控网络中的差异表达基因。测量不同组织样本中 miR-16-5p 的表达和四个关键基因甲基化状态的变化。 : 我们发现，GSE54129 包含 21 个正常胃组织和 111 个胃癌组织，GSE164174 包含 1417 个正常胃组织和 1423 个胃癌组织。Venn 图分析结果显示，与对照组相比，GSE54129 和 GSE164174 数据集共有 68 个 DEmiRNAs 上调，且未发现共同下调的 DEmiRNAs。进一步分析 GSE108345 数据集，我们获得了与 TLR 激活相关的竞争内源性 RNA (ceRNA) 网络，并列出了前 10 个 lncRNA-miRNA-mRNA 网络，其中包含 10 个 miRNA、86 个 mRNA 和 134 个 lncRNA。细胞 HuBBA 评分共获得 1 个 miRNA、16 个 mRNA 和 45 个 lncRNA，其中 miR-16-5p 得分最高，因为它被认为是 GC 细胞中 TLR 激活的关键 miRNA，对微生物的抵抗很重要。京都基因与基因组百科全书 (KEGG) 分析结果表明，内吞作用、癌症中的 microRNAs 和 PI3K-Akt 信号通路与 TLR 信号有关。体内实验结果表明，miR-16-5p 在胃癌细胞和组织中高表达。 : Hsa-miR-16-5p 的靶基因主要通过调节 MCL1、AP2B1、LAMB1 和 RAB11FIP2 这四个基因的表达发挥作用。这些发现为 GC 的免疫治疗提供了科学依据。
