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在肝细胞中增加的PRP19阻碍了B细胞功能以促进肝癌发生

Zhiyong Liu¹, Xiahui Lin¹, Danying Zhang¹

¹Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Disease, Zhongshan Hospital, Fudan University, Shanghai, 200030, China.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)

|October 18, 2024

概括

研究人员确定了前mRNA处理因子19 (PRP19) 作为肝细胞癌 (HCC) 的关键调节者. 抑制PRP19可以增强B细胞的透,阻碍瘤生长,并为HCC提供新的免疫治疗策略.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

瘤免疫微环境显著影响肝细胞癌 (HCC) 恶性.
在HCC免疫微环境中,B细胞的特定作用和调节机制尚不清楚.

研究的目的:

为了研究HCC中B细胞的免疫功能.
通过比较B细胞高透和低透的HCC组织,确定B细胞透HCC的关键调节者.

主要方法:

具有不同B细胞透水平的HCC组织之间的基因表达差异分析.
在HCC模型中抑制前mRNA处理因子19 (PRP19) 表达.
同免疫沉 (Co-IP) 测试以确定蛋白质相互作用.
在小鼠模型中评估B细胞透,瘤生长和免疫反应.
分析PRP19,DDX5和B细胞透作为预后指标.

主要成果:

在低B细胞透率的HCC组织中,PRP19表达升高,与B细胞标记物CD20负相关.
抑制PRP19增加了瘤中的B细胞透,并抑制了HCC的进展.
PRP19与DEAD-box酶5 (DDX5) 相互作用,促进其无处不在和降解.
降低的DDX5水平损害了CXCL12mRNA的稳定性,通过CXCL12/CXCR4轴抑制了B细胞的招募和血细胞的分化.
通过采用CXCR4+B细胞与CXCL12治疗的移植,在小鼠中抑制了HCC的发展.

结论:

通过向DDX5和CXCL12/CXCR4轴,PRP19作为HCC中B细胞透的负调节剂.
对于HCC患者来说,PRP19,DDX5和B细胞透水平是重要的预后指标.
向PRP19和调节瘤透B细胞功能是HCC免疫疗法的有希望的策略.

关键词:

预-mRNA处理因子19 预-mRNA处理因子肝细胞癌是肝细胞癌.免疫反应的免疫反应.瘤微环境是一个微环境.瘤透的B细胞

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