Zhang Tianmiao, Zhang Rongcheng, Zhang Zhongqi, Li Di, Guo Xuefeng, Zhang Zhengbao, Zhu Xiaonian, Tan Shengkui
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi, China.
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi, China.
Int Immunopharmacol. 2024 Mar 30;130:111740. doi: 10.1016/j.intimp.2024.111740. Epub 2024 Feb 23.
As a homologous counterpart to the prokaryotic oligonuclease found in the cellular cytoplasm and mitochondrion, REXO2 assumes a pivotal role in the maintenance of mitochondrial homeostasis. Nevertheless, the precise functions and mechanisms by which REXO2 operates within the context of hepatocellular carcinoma (HCC) have hitherto remained unexamined.
The expression levels of REXO2 in HCC tissues were evaluated through the utilization of the immunohistochemical (IHC) method, and subsequently, the association between REXO2 expression and the clinicopathological characteristics of HCC patients was scrutinized employing the χ test. A battery of experimental assays, encompassing CCK8 viability assessment, cell colony formation, wound healing, and transwell assays, were conducted with the aim of elucidating the biological role of REXO2 within HCC cells. Complementary bioinformatics analyses were undertaken to discern potential correlations between REXO2 and immune infiltration in tumor tissues.
Our IHC findings have unveiled a notable up-regulation of REXO2 within HCC tissues, and this heightened expression bears the status of an independent prognostic factor, portending an adverse outcome for HCC patients (P < 0.05). Upon the attenuation of REXO2 expression, a discernible reduction in the rates of proliferation, invasion and migration of HCC cells ensued (P < 0.05). Furthermore, transcriptome sequencing analysis has provided insights into the putative influence of REXO2 on the development of HCC through the modulation of TNF and NF-κB signaling pathways. Additionally, our bioinformatics analyses have demonstrated a positive correlation between REXO2 and tumor immune cell infiltration, as well as immune checkpoint CTLA-4.
In summation, our results posit an association between the up-regulation of REXO2 and adverse prognostic outcomes, alongside the involvement of immune-related signaling pathways and tumor immune infiltration within the realm of HCC.
作为在细胞质和线粒体中发现的原核寡核苷酸酶的同源对应物,REXO2在维持线粒体稳态中起关键作用。然而,REXO2在肝细胞癌(HCC)背景下发挥作用的精确功能和机制迄今仍未得到研究。
通过免疫组织化学(IHC)方法评估HCC组织中REXO2的表达水平,随后采用χ检验研究REXO2表达与HCC患者临床病理特征之间的关联。进行了一系列实验分析,包括CCK8活力评估、细胞集落形成、伤口愈合和Transwell分析,以阐明REXO2在HCC细胞中的生物学作用。进行了补充生物信息学分析,以识别REXO2与肿瘤组织中免疫浸润之间的潜在相关性。
我们的IHC研究结果揭示了HCC组织中REXO2的显著上调,这种高表达具有独立预后因素的地位,预示着HCC患者的不良预后(P < 0.05)。REXO2表达减弱后,HCC细胞的增殖、侵袭和迁移率明显降低(P < 0.05)。此外,转录组测序分析通过调节TNF和NF-κB信号通路,为REXO2对HCC发展的假定影响提供了见解。此外,我们的生物信息学分析表明REXO2与肿瘤免疫细胞浸润以及免疫检查点CTLA-4之间存在正相关。
总之,我们的结果表明REXO2上调与不良预后结果之间存在关联,同时免疫相关信号通路和肿瘤免疫浸润参与了HCC领域。