Increased PRP19 in Hepatocyte Impedes B Cell Function to Promote Hepatocarcinogenesis

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• The tumor immune microenvironment significantly influences hepatocellular carcinoma (HCC) malignancy.
• The specific roles and regulatory mechanisms of B cells within the HCC immune microenvironment are not well understood.

Purpose of the Study:

• To investigate the immune function of B cells in HCC.
• To identify key regulators of B cell infiltration in HCC by comparing B cell high- and low-infiltrated HCC tissues.

Main Methods:

• Differential gene expression analysis between HCC tissues with varying B cell infiltration levels.
• Inhibition of Pre-mRNA processing factor 19 (PRP19) expression in HCC models.
• Co-immunoprecipitation (Co-IP) assays to determine protein interactions.
• Assessment of B cell infiltration, tumor growth, and immune response in mouse models.
• Analysis of PRP19, DDX5, and B cell infiltration as prognostic indicators.

Main Results:

• PRP19 expression was elevated in HCC tissues with low B cell infiltration and negatively correlated with the B cell marker CD20.
• Inhibiting PRP19 increased B cell infiltration in tumors and suppressed HCC progression.
• PRP19 interacts with DEAD-box helicase 5 (DDX5), promoting its ubiquitination and degradation.
• Reduced DDX5 levels impaired CXCL12 mRNA stability, suppressing B cell recruitment and plasma cell differentiation via the CXCL12/CXCR4 axis.
• Adoptive transfer of CXCR4+ B cells with CXCL12 treatment inhibited HCC development in mice.

Conclusions:

• PRP19 acts as a negative regulator of B cell infiltration in HCC by targeting DDX5 and the CXCL12/CXCR4 axis.
• PRP19, DDX5, and B cell infiltration levels are significant prognostic indicators for HCC patients.
• Targeting PRP19 and modulating tumor-infiltrating B cell function presents a promising strategy for HCC immunotherapy.