IRF5 promotes glycolysis in the progression of hepatocellular carcinoma and is regulated by TRIM35.

Autor: Fang Y; Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China., Lu ZH; Department of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai, China., Liu BZ; Department of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai, China., Li N; Department of Hepatic Surgery I (Ward I), Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China., Yang MZ; Department of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai, China., Wang P; Department of Rehabilitation, Zhongshan Hospital, Fudan University, Shanghai, China.
Jazyk: angličtina
Zdroj: Journal of digestive diseases [J Dig Dis] 2023 Aug-Sep; Vol. 24 (8-9), pp. 480-490. Date of Electronic Publication: 2023 Sep 19.
DOI: 10.1111/1751-2980.13218
Abstrakt: Objectives: 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).
Methods: 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.
Results: 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.
Conclusion: 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.
(© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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