Chen Wanjin, Liu Kailin, Wang Zhiling, Zhang Hui, Tan Ming, Liu Yuting, Gao Tingting, Su Xiameng, Gu Leirong, Chen Xinyan, Cheng Shengtao
Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, 400016, China.
Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, China.
Apoptosis. 2025 Mar 27. doi: 10.1007/s10495-025-02103-2.
To clarify the biological functions and prognostic significance of migrasome-related integrin subunit alpha 5 (ITGA5) in hepatocellular carcinoma (HCC). We used The Cancer Genome Atlas datasets and RNA-seq data from nine sets of paired HCC and adjacent normal tissues to identify key migrasome-related genes through a comprehensive analysis and weighted correlation network analysis. We then confirmed their roles in HCC through analyses of gene mutations, methylation, and immune cell infiltration, as well as molecular docking, molecular dynamics, and cell experiments. A comprehensive analysis of migrasome-related genes showed that ITGA5 was a critical gene related to HCC, and it is highly expressed in HCC tissues, which is related to poor prognosis. Further enrichment analysis revealed that ITGA5 is involved in many pathways related to tumor occurrence and metastasis, such as the PI3K-AKT pathway. In addition, ITGA5 was found to be expressed in multiple types of immune cells and was closely associated with immune infiltration. Drug sensitivity, molecular docking, and molecular dynamics analyses indicated that ITGA5 may enhance the sensitivity of HCC to drug TGX221. Finally, cell phenotype experiments confirmed that ITGA5 knockdown suppressed the proliferation, migration, and invasion of HCC cells, and while overexpression exacerbated malignant phenotypes. Our analyses showed that ITGA5 is a key migrasome-related gene involved in the proliferation and metastasis of HCC that has promise as a therapeutic target and candidate prognostic indicator.
为了阐明迁移体相关整合素亚基α5（ITGA5）在肝细胞癌（HCC）中的生物学功能及预后意义。我们使用了癌症基因组图谱数据集以及来自9组配对的HCC组织和癌旁正常组织的RNA测序数据，通过综合分析和加权相关网络分析来鉴定关键的迁移体相关基因。然后，我们通过基因突变、甲基化、免疫细胞浸润分析以及分子对接、分子动力学和细胞实验来证实它们在HCC中的作用。对迁移体相关基因的综合分析表明，ITGA5是与HCC相关的关键基因，在HCC组织中高表达，这与预后不良相关。进一步的富集分析显示，ITGA5参与许多与肿瘤发生和转移相关的途径，如PI3K-AKT途径。此外，发现ITGA5在多种免疫细胞中表达，并与免疫浸润密切相关。药物敏感性、分子对接和分子动力学分析表明，ITGA5可能增强HCC对药物TGX221的敏感性。最后，细胞表型实验证实，ITGA5基因敲低抑制了HCC细胞的增殖、迁移和侵袭，而过表达则加剧了恶性表型。我们的分析表明，ITGA5是参与HCC增殖和转移的关键迁移体相关基因，有望成为治疗靶点和候选预后指标。
