Expression and prognostic value of PRDX family in colon adenocarcinoma by integrating comprehensive analysis and in vitro and in vivo validation.

Expression and prognostic value of PRDX family in colon adenocarcinoma by integrating comprehensive analysis and in vitro and in vivo validation.
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DOI:
10.3389/fonc.2023.1136738
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发表时间:
2023
影响因子:
4.7
通讯作者:
--
中科院分区:
医学3区
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氧化还原蛋白家族是氧化还原反应的重要调节因子,与多种肿瘤的发生密切相关。然而,peroxiredoxin4(PRDX4)在结肠腺癌(COAD)中的作用仍然知之甚少。多中心数据库,包括GEPIA、HPA、UALCAN、cBioPortal、cancerSEA、STRING、CCLE和LinkedOmics,全面分析了COAD患者PRDX的转录表达、预后价值、遗传改变、信号通路和相关基因。进行集落形成、transwell、流式细胞术、球体形成和异种移植物测定以进一步在体外和体内验证。PRDX家族的成员在COAD中差异表达,每个成员都表现出不同程度的遗传改变。有趣的是,只有PRDX4与COAD预后和分期显著相关。单细胞测序结果表明PRDX4与细胞增殖、凋亡和侵袭呈正相关,而与干细胞性呈负相关。此外,PRDX4还参与细胞生长等一系列重要的生物学过程。此外,体内和体外分析表明,敲低PRDX4抑制HCT 116细胞的增殖和侵袭,同时促进凋亡和干细胞。我们确定PRDX4表达是COAD的一种新的潜在预后标志物。
The peroxiredoxin family, a crucial regulator of redox reactions, is strongly associated with various tumorigenesis. However, the role of peroxiredoxin4 (PRDX4) in colon adenocarcinoma (COAD) remains poorly understood. Multicenter databases, including GEPIA, HPA, UALCAN, cBioPortal, cancerSEA, STRING, CCLE, and LinkedOmics, comprehensively analyzed transcriptional expression, prognostic value, genetic alterations, signaling pathways, and associated genes of the PRDXs in COAD patients. Colony formation, transwell, flow cytometry, sphere formation, and xenograft assays were performed to validate further in vitro and in vivo. Members of the PRDX family were differentially expressed in COAD, with each member showing varying degrees of genetic alterations. Intriguingly, only PRDX4 significantly correlated with COAD prognosis and stage. The single-cell sequencing suggested that PRDX4 is positively correlated with proliferation, apoptosis, and invasion, whereas negatively correlated with stemness. Moreover, PRDX4 involved in a series of critical biological processes, such as cell growth. Furthermore, in vivo and in vitro analyses indicated that knocking down PRDX4 inhibits the proliferation and invasion of HCT116 cells while promoting apoptosis and stemness. We identified PRDX4 expression as a novel potential prognostic marker in COAD.
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