胆囊癌（GBC）是一种致命的疾病，手术切除是唯一的治疗方法。然而，许多患者不适合手术，目前的辅助治疗效果有限。新一代测序提高了我们对癌症分子途径的理解，激发了人们对基于 microRNA 的基因调控的兴趣。该研究的目的是识别 GBC 中失调的 miRNA，并研究它们作为有效和有针对性的治疗策略的治疗工具的潜力。使用 Illumina HiSeq 平台对 GBC 和对照组织样本的 miRNA 表达进行测序。使用 Panther 和 Gene Ontology 数据库确定生物过程和相关途径。鉴定出439个显着差异表达的miRNA；其中19个上调，29个下调。关键丰富的生物过程包括免疫细胞凋亡、内质网（ER）超载反应和雄激素受体（AR）信号通路的负调节。 Panther 分析显示，胰岛素样生长因子 (IGF)-丝裂原激活蛋白激酶 (MAPK) 级联、p38 MAPK 通路、p53 通路和 FAS（肿瘤坏死因子受体的一个亚组）信号通路在失调的 miRNA 中高度富集。克尔斯滕大鼠肉瘤病毒（KRAS）、AR和干扰素γ（IFN-γ）途径被确定为可能适合靶向治疗的关键途径。我们的结论是，涉及基于 miRNA 的干预措施的组合方法可以增强治疗效果。我们的研究强调精准医学的重要性，利用有义和反义 miRNA 作为 GBC 中潜在疗法的靶向途径。© 2023。作者。

Gallbladder cancer (GBC) is a lethal disease with surgical resection as the only curative treatment. However, many patients are ineligible for surgery, and current adjuvant treatments exhibit limited effectiveness. Next-generation sequencing has improved our understanding of molecular pathways in cancer, sparking interest in microRNA-based gene regulation. The aim of the study is to identify dysregulated miRNAs in GBC and investigate their potential as therapeutic tools for effective and targeted treatment strategies. GBC and control tissue samples were sequenced for miRNA expression using the Illumina HiSeq platform. Biological processes and related pathways were determined using the Panther and Gene Ontology databases. 439 significantly differentially expressed miRNAs were identified; 19 of them were upregulated and 29 were downregulated. Key enriched biological processes included immune cell apoptosis, endoplasmic reticulum (ER) overload response, and negative regulation of the androgen receptor (AR) signaling pathway. Panther analysis revealed the insulin-like growth factor (IGF)-mitogen activated protein kinases (MAPK) cascade, p38 MAPK pathway, p53 pathway, and FAS (a subgroup of the tumor necrosis factor receptor) signaling pathway as highly enriched among dysregulated miRNAs. Kirsten rat sarcoma virus (KRAS), AR, and interferon gamma (IFN-γ) pathways were identified among the key pathways potentially amenable to targeted therapy. We concluded that a combination approach involving miRNA-based interventions could enhance therapeutic outcomes. Our research emphasizes the importance of precision medicine, targeting pathways using sense and anti-sense miRNAs as potential therapies in GBC.© 2023. The Author(s).