Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai, China.
J Dig Dis. 2023 Aug-Sep;24(8-9):480-490. doi: 10.1111/1751-2980.13218. Epub 2023 Sep 19.
The interferon regulatory factor (IRF) family of proteins are involved in tumor progression. However, the role of IRF5 in tumorigenesis remains unknown. In this study we aimed to elucidate the functions of IRF5 in the progression of hepatocellular carcinoma (HCC).
IRF5 expression in HCC was analyzed through quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry (IHC), etc. The Cell Counting Kit 8 (CCK8) assay, anchorage-independent assay, and EdU assay were used to evaluate the role of IRF5. The molecular mechanisms were studied by analyzing the metabolites with mass spectrum and immunoprecipitation.
IRF5 was upregulated in HCC. Interfering with IRF5 inhibited the proliferation and tumorigenic potential of HCC cells. When studying the molecular mechanism, IRF5 was found to upregulate the expression of lactate dehydrogenase A (LDHA) and promoted glycolysis. Additionally, tripartite motif containing 35 (TRIM35) interacted with IRF5, promoting its ubiquitination and degradation. In the clinically obtained HCC samples, TRIM35 was negatively correlated with the expression of IRF5.
These findings reveal the oncogenic function of IRF5 in the progression of HCC by enhancing glycolysis, further supporting the potential of IRF5 as a viable target for HCC therapy.
干扰素调节因子（IRF）家族蛋白参与肿瘤进展。然而，IRF5 在肿瘤发生中的作用尚不清楚。本研究旨在阐明 IRF5 在肝细胞癌（HCC）进展中的作用。
通过定量聚合酶链反应（qPCR）、western blot 和免疫组织化学（IHC）等方法分析 HCC 中 IRF5 的表达。使用细胞计数试剂盒 8（CCK8）检测、非依赖性附着检测和 EdU 检测评估 IRF5 的作用。通过质谱分析和免疫沉淀研究分子机制。
IRF5 在 HCC 中上调。干扰 IRF5 抑制 HCC 细胞的增殖和致瘤潜能。在研究分子机制时，发现 IRF5 上调了乳酸脱氢酶 A（LDHA）的表达，促进了糖酵解。此外，三结构域蛋白 35（TRIM35）与 IRF5 相互作用，促进其泛素化和降解。在临床获得的 HCC 样本中，TRIM35 与 IRF5 的表达呈负相关。
这些发现揭示了 IRF5 通过增强糖酵解在 HCC 进展中的致癌功能，进一步支持了将 IRF5 作为 HCC 治疗潜在靶点的可能性。
