Jin Wen, Liu Jianli, Yang Tingyu, Feng Zongqi, Yang Jie, Cao Lei, Wu Chengyan, Zuo Yongchun, Yu Lan
Clinical Medical Research Center/Inner Mongolia Key Laboratory of Gene Regulation of the Metabolic Disease, Inner Mongolia People's Hospital, Hohhot, China.
School of Water Resource and Environment Engineering, China University of Geosciences, Beijing, China.
IET Syst Biol. 2025 Jan-Dec;19(1):e70014. doi: 10.1049/syb2.70014.
MicroRNAs (miRNAs) are crucial factors in gene regulation, and their dysregulation plays important roles in the immunity of gastric cancer (GC). However, finding specific and effective miRNA markers is still a great challenge for GC immunotherapy. In this study, we computed and analysed miRNA-seq, RNA-seq and clinical data of GC patients from the TCGA database. With the comparison of tumour and normal tissues in GC, we identified 2056 upregulated and 2311 downregulated protein-coding genes. Based on the miRNet database, more than 2600 miRNAs interact with these genes. Several key miRNAs, including hsa-mir-34a, hsa-mir-182 and hsa-mir-23b, were identified to potentially play important regulatory roles in the expression of most upregulated and downregulated genes in GC. Based on bioinformation approaches, the expressions of hsa-mir-34a and hsa-mir-182 were closely linked to the tumour stage, and high expression of hsa-mir-23b was correlated with poor survival in GC. Moreover, these three miRNAs are involved in immune cell infiltration (such as activated memory CD4 T cells and resting mast cells), particularly hsa-mir-182 and hsa-mir-23b. GSEA suggested that the changes in their expression may possibly activate/inhibit immune-related signal pathways, such as chemokine signalling pathway and CXCR4 pathway. These results will provide possible miRNA markers or targets for combined immunotherapy of GC.
微小RNA(miRNA)是基因调控中的关键因素,其失调在胃癌(GC)免疫中起重要作用。然而,寻找特异性和有效的miRNA标志物仍是GC免疫治疗的一大挑战。在本研究中,我们计算并分析了来自TCGA数据库的GC患者的miRNA测序、RNA测序和临床数据。通过比较GC中的肿瘤组织和正常组织,我们鉴定出2056个上调和2311个下调的蛋白质编码基因。基于miRNet数据库,超过2600个miRNA与这些基因相互作用。确定了几个关键的miRNA,包括hsa-mir-34a、hsa-mir-182和hsa-mir-23b,它们可能在GC中大多数上调和下调基因的表达中发挥重要调控作用。基于生物信息学方法,hsa-mir-34a和hsa-mir-182的表达与肿瘤分期密切相关,hsa-mir-23b的高表达与GC患者的不良生存相关。此外,这三种miRNA参与免疫细胞浸润(如活化记忆CD4 T细胞和静息肥大细胞),特别是hsa-mir-182和hsa-mir-23b。基因集富集分析(GSEA)表明,它们表达的变化可能激活/抑制免疫相关信号通路,如趋化因子信号通路和CXCR4通路。这些结果将为GC的联合免疫治疗提供可能的miRNA标志物或靶点。