Overexpression of RBM34 Promotes Tumor Progression and Correlates with Poor Prognosis of Hepatocellular Carcinoma.
Overexpression of RBM34 Promotes Tumor Progression and Correlates with Poor Prognosis of Hepatocellular Carcinoma.
复制标题
DOI：
10.14218/jcth.2022.00166
复制
发表时间：
2023-04-28
影响因子：
3.6
通讯作者：
中科院分区：
文献类型：
--
作者：
新的证据表明，RNA结合基序(RBM)蛋白参与了肝癌的发生，并作为癌基因或肿瘤抑制因子发挥作用。本研究的目的是探讨RBM蛋白RBM34在肝细胞癌中的作用。我们首先检查了RBM34在不同癌症中的表达。探讨RBM34与肝细胞癌临床病理特征的相关性及对肝细胞癌预后的判断价值。对RBM34相关差异表达基因(DEG)进行功能浓缩分析，探讨其生物学功能。RNA测序(RNA-seq)用于确定影响RBM34基因敲除的下游基因和途径。并分析了RBM34与免疫特性的相关性。在体外和体内实验中检测了RBM34的致癌作用。RBM34在肝细胞癌中高表达，与临床病理特征及预后相关。RBM34与肿瘤免疫细胞浸润、免疫细胞生物标志物、免疫检查点表达呈正相关。RBM34、T细胞耗竭和调节性T细胞标记基因之间也存在正相关。RBM34基因敲除显著抑制了细胞的增殖、迁移和异种移植瘤的生长，并使肝癌细胞对索拉非尼治疗敏感。RBM34抑制肝癌细胞中FGFR2的表达并影响PI3K-AKT通路的激活。我们的研究提示，RBM34可能成为一种新的肝细胞癌预后指标和治疗靶点。
Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study was to investigate the role of RBM34, an RBM protein, in hepatocellular carcinoma (HCC). We first examined the expression of RBM34 across cancers. The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated. Functional enrichment analysis of RBM34-related differentially expressed genes (DEGs) was performed to explore its biological function. RNA sequencing (RNA-seq) was applied to identify downstream genes and pathways affected upon RBM34 knockout. The correlation of RBM34 with immune characteristics was also analyzed. The oncogenic function of RBM34 was examined in in vitro and in vivo experiments. RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis. RBM34 was positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. A positive correlation was also observed between RBM34, T cell exhaustion, and regulatory T cell marker genes. Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells. Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.