1. Increased PRP19 in Hepatocyte Impedes B Cell Function to Promote Hepatocarcinogenesis.
- Author
-
Liu Z, Lin X, Zhang D, Guo D, Tang W, Yu X, Zhang F, Zhang S, Xue R, Shen X, and Dong L
- Subjects
- Animals, Mice, Humans, Hepatocytes metabolism, Tumor Microenvironment immunology, Tumor Microenvironment genetics, Disease Models, Animal, RNA Splicing Factors genetics, RNA Splicing Factors metabolism, Carcinogenesis genetics, Carcinogenesis immunology, Chemokine CXCL12 metabolism, Chemokine CXCL12 genetics, Male, Liver Neoplasms genetics, Liver Neoplasms immunology, Liver Neoplasms metabolism, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular immunology, Carcinoma, Hepatocellular metabolism, B-Lymphocytes immunology, B-Lymphocytes metabolism
- Abstract
Tumor immune microenvironment is strongly associated with the malignancy behavior of hepatocellular carcinoma (HCC). However, the immune function and regulatory mechanisms of B cells in HCC remain unclear. The expression differences between B cell high- and low-infiltration HCC samples are explored to identify the key regulator. Pre-mRNA processing factor 19 (PRP19) expression is increased in B cell low-infiltrated tissues and negatively correlated with the B cell marker, CD20. Inhibition of PRP19 expression promoted B cell infiltration in tumor tissue and impeded HCC growth. Mechanically, the co-immunoprecipitation (Co-IP) assay revealed that PRP19 interacts with DEAD-box helicase 5 (DDX5), leading to ubiquitination and degradation of the DDX5 protein. The attenuated DDX5 impairs CXCL12 mRNA stability to suppress B cell recruitment and plasma cell differentiation via CXCL12/CXCR4 axis. Moreover, the adoptive transfer of CXCR4+ B cells combined with CXCL12 treatment in mice models effectively inhibits HCC development by reshaping the immune response. The expression of PRP19, DDX5, and infiltrating B cells are recognized as clinical prognosis indicators for HCC patients. Overall, this study provides valuable insights into the clinical benefits of HCC immunotherapy by targeting PRP19 and modulating tumor-infiltrating B cell immune function., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
- Full Text
- View/download PDF