Increased PRP19 in Hepatocyte Impedes B Cell Function to Promote Hepatocarcinogenesis

Increased PRP19 in Hepatocyte Impedes B Cell Function to Promote Hepatocarcinogenesis

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...

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Bibliographic Details
Main Authors: Zhiyong Liu, Xiahui Lin, Danying Zhang, Dezhen Guo, Wenqing Tang, Xiangnan Yu, Feng Zhang, Si Zhang, Ruyi Xue, Xizhong Shen, Ling Dong
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
Subjects:
hepatocellular carcinoma
immune response
Pre‐mRNA processing factor 19
tumor microenvironment
tumor‐infiltrating B cells
Online Access:https://doi.org/10.1002/advs.202407517
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Summary: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.
ISSN:2198-3844

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