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NUF2 作为一种新的肿瘤干细胞标志物促进乳腺癌的发展。

NUF2 Promotes Breast Cancer Development as a New Tumor Stem Cell Indicator.

机构信息

Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan 430081, China.

出版信息

Int J Mol Sci. 2023 Feb 20;24(4):4226. doi: 10.3390/ijms24044226.

Abstract

Multiple new subtypes of breast cancer (BRCA) are identified in women each year, rendering BRCA the most common and rapidly expanding form of cancer in females globally. NUF2 has been identified as a prognostic factor in various human cancers, regulating cell apoptosis and proliferation. However, its role in BRCA prognosis has not been clarified. This study explored the role of NUF2 in breast cancer development and prognosis using informatic analysis combined with in vivo intracellular studies. Through the online website TIMER, we evaluated the transcription profile of NUF2 across a variety of different cancer types and found that NUF2 mRNA was highly expressed in BRCA patients. Its transcription level was found to be related to the subtype, pathological stage, and prognosis of BRCA. The R program analysis showed a correlation of NUF2 with cell proliferation and tumor stemness in the BRCA patient samples. Subsequently, the association between the NUF2 expression level and immune cell infiltration was analyzed using the XIANTAO and TIMER tools. The results revealed that NUF2 expression was correlated with the responses of multiple immune cells. Furthermore, we observed the effect of NUF2 expression on tumor stemness in BRCA cell lines in vivo. The experimental results illuminated that the overexpression of NUF2 statistically upregulated the proliferation and tumor stemness ability of the BRCA cell lines MCF-7 and Hs-578T. Meanwhile, the knockdown of NUF2 inhibited the abilities of both cell lines, a finding which was verified by analyzing the subcutaneous tumorigenic ability in nude mice. In summary, this study suggests that NUF2 may play a key role in the development and progression of BRCA by affecting tumor stemness. As a stemness indicator, it has the potential to be one of the markers for the diagnosis of BRCA.

摘要

每年都会在女性中发现多种新的乳腺癌 (BRCA) 亚型,使 BRCA 成为全球女性中最常见且迅速扩展的癌症类型。NUF2 已被确定为各种人类癌症的预后因素,调节细胞凋亡和增殖。然而,其在 BRCA 预后中的作用尚未阐明。本研究通过体内细胞内研究与信息分析相结合,探讨了 NUF2 在乳腺癌发生和预后中的作用。通过在线网站 TIMER,我们评估了 NUF2 在多种不同癌症类型中的转录谱,发现 NUF2 mRNA 在 BRCA 患者中高表达。其转录水平与 BRCA 的亚型、病理分期和预后有关。R 程序分析显示 NUF2 与 BRCA 患者样本中的细胞增殖和肿瘤干性相关。随后,使用 XIANTAO 和 TIMER 工具分析了 NUF2 表达水平与免疫细胞浸润的相关性。结果表明,NUF2 表达与多种免疫细胞的反应相关。此外,我们观察了 NUF2 表达对 BRCA 细胞系体内肿瘤干性的影响。实验结果表明,NUF2 的过表达在统计学上可上调 BRCA 细胞系 MCF-7 和 Hs-578T 的增殖和肿瘤干性能力。同时,NUF2 的敲低抑制了这两个细胞系的能力,这一发现通过分析裸鼠皮下致瘤能力得到了验证。总之,本研究表明,NUF2 可能通过影响肿瘤干性在 BRCA 的发生和发展中发挥关键作用。作为干性标志物,它有可能成为 BRCA 诊断的标志物之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb7d/9965662/c80fe58a97ef/ijms-24-04226-g001.jpg

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