The Role of NOL3 in Colon Adenocarcinoma Metastasis and Its Association With DNA Methylation

IF 3.7 2区 医学 Q2 GENETICS & HEREDITY
Li Hong, Hao Zhang, Ruipeng Wang, Zirui Zhuang, Jinjing Xu, Youyuan Tang
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Abstract

Colon adenocarcinoma (COAD) is a particularly aggressive cancer type, frequently identified at a later stage. Thus, it is crucial to enhance our understanding of the fundamental mechanisms that govern COAD cellular behavior and to perform extensive research into the biological foundations underlying its development, progression, invasion, and metastasis. We initially discovered NOL3 as a significant gene influencing COAD metastasis through the application of the weighted gene coexpression network analysis algorithm using the TCGA-COAD dataset. This was succeeded by an assessment of NOL3’s expression levels and prognostic significance. Moreover, we investigated the biological roles of NOL3 utilizing transcriptomic data. Our results demonstrate significant associations between NOL3 and immune infiltration in COAD, as well as sensitivity to chemotherapy. Furthermore, we utilized the tumor immune dysfunction and exclusion (TIDE) algorithm to evaluate how various cohorts responded to immune checkpoint therapies. Ultimately, the influence of NOL3 on the metastasis of COAD cells was confirmed through in vitro experiments. Our results indicate that NOL3 can promote COAD metastasis, and its underlying mechanism may be associated with DNA methylation. In summary, NOL3 has been identified by us as a key biomarker for COAD metastasis.

Abstract Image

NOL3在结肠癌转移中的作用及其与DNA甲基化的关系
结肠腺癌(COAD)是一种特别具有侵袭性的癌症类型,通常在晚期才被发现。因此,加强我们对控制COAD细胞行为的基本机制的理解,并对其发生、进展、侵袭和转移的生物学基础进行广泛的研究是至关重要的。我们利用TCGA-COAD数据集,应用加权基因共表达网络分析算法,初步发现NOL3是影响COAD转移的重要基因。随后评估NOL3的表达水平和预后意义。此外,我们利用转录组学数据研究了NOL3的生物学作用。我们的研究结果表明,在COAD中,NOL3与免疫浸润以及对化疗的敏感性之间存在显著关联。此外,我们利用肿瘤免疫功能障碍和排斥(TIDE)算法来评估不同队列对免疫检查点疗法的反应。最终,通过体外实验证实了NOL3对COAD细胞转移的影响。我们的研究结果表明,NOL3可以促进COAD的转移,其潜在机制可能与DNA甲基化有关。综上所述,我们已经确定NOL3是COAD转移的关键生物标志物。
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来源期刊
Human Mutation
Human Mutation 医学-遗传学
CiteScore
8.40
自引率
5.10%
发文量
190
审稿时长
2 months
期刊介绍: Human Mutation is a peer-reviewed journal that offers publication of original Research Articles, Methods, Mutation Updates, Reviews, Database Articles, Rapid Communications, and Letters on broad aspects of mutation research in humans. Reports of novel DNA variations and their phenotypic consequences, reports of SNPs demonstrated as valuable for genomic analysis, descriptions of new molecular detection methods, and novel approaches to clinical diagnosis are welcomed. Novel reports of gene organization at the genomic level, reported in the context of mutation investigation, may be considered. The journal provides a unique forum for the exchange of ideas, methods, and applications of interest to molecular, human, and medical geneticists in academic, industrial, and clinical research settings worldwide.
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