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结肠癌组织中 ADAD1、DMRTC2、PRSS54、SYCE1、SYCP1、TEX101、TEX48 和 TMPRSS12 基因谱的差异表达及调控及其对表观遗传药物的体外反应。

Differential expression and regulation of ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12 gene profiles in colon cancer tissues and their in vitro response to epigenetic drugs.

机构信息

Zoology Department, College of Science, King Saud University, Riyadh, Saudi Arabia.

Laboratories Directorate, General Directorate of Animal Health, Ministry Deputyship for Agriculture, Ministry of Environment, Water and Agriculture, Riyadh, Saudi Arabia.

出版信息

PLoS One. 2024 Aug 29;19(8):e0307724. doi: 10.1371/journal.pone.0307724. eCollection 2024.

DOI:10.1371/journal.pone.0307724
PMID:39208330
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11361649/
Abstract

Colon cancer (CC) is a significant cause of death worldwide, particularly in Saudi Arabia. To increase the accuracy of diagnosis and treatment, it is important to discover new specific biomarkers for CC. The main objectives of this research are to identify potential specific biomarkers for the early diagnosis of CC by analyzing the expressions of eight cancer testis (CT) genes, as well as to analyze how epigenetic mechanisms control the expression of these genes in CC cell lines. Tissue samples were collected from 15 male patients with CC tissues and matched NC tissues for gene expression analysis. The expression levels of specific CT genes, including ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12, were assessed using quantitative techniques. To validate the gene expression patterns, we used publicly available CC statistics. To investigate the effect of inhibition of DNA methylation and histone deacetylation on CT gene expression, in vitro experiments were performed using HCT116 and Caco-2 cell lines. There was no detected expression of the genes neither in the patient samples nor in NC tissues, except for TEX48, which exhibited upregulation in CC samples compared to NC tissues in online datasets. Notably, CT genes showed expression in testis samples. In vitro, experiments demonstrated significant enhancement in mRNA expression levels of ADAD1, DMRTC2, PRSS54, SYCE1, SYCP1, TEX101, TEX48, and TMPRSS12 following treatment with 5-aza-2'-deoxycytidine and trichostatin A in HCT116 and Caco-2 cell lines. Epigenetic treatments modify the expression of CT genes, indicating that these genes can potentially be used as biomarkers for CC. The importance of conducting further research to understand and target epigenetic mechanisms to improve CC treatment cannot be overemphasized.

摘要

结肠癌(CC)是全球范围内导致死亡的一个重要原因,尤其是在沙特阿拉伯。为了提高 CC 的诊断和治疗的准确性,发现新的 CC 特异性生物标志物是非常重要的。本研究的主要目的是通过分析八个癌症睾丸(CT)基因的表达,鉴定潜在的 CC 早期诊断特异性生物标志物,并分析表观遗传机制如何控制 CC 细胞系中这些基因的表达。收集了 15 名男性 CC 组织和匹配的 NC 组织的患者的组织样本,进行基因表达分析。使用定量技术评估了 ADAD1、DMRTC2、PRSS54、SYCE1、SYCP1、TEX101、TEX48 和 TMPRSS12 等特定 CT 基因的表达水平。为了验证基因表达模式,我们使用了公开的 CC 统计数据。为了研究抑制 DNA 甲基化和组蛋白去乙酰化对 CT 基因表达的影响,我们在 HCT116 和 Caco-2 细胞系中进行了体外实验。除了 TEX48 基因在在线数据集的 CC 样本中相对于 NC 组织上调外,患者样本和 NC 组织中均未检测到这些基因的表达。值得注意的是,CT 基因在睾丸样本中表达。体外实验表明,在 HCT116 和 Caco-2 细胞系中,用 5-aza-2'-脱氧胞苷和曲古抑菌素 A 处理后,ADAD1、DMRTC2、PRSS54、SYCE1、SYCP1、TEX101、TEX48 和 TMPRSS12 的 mRNA 表达水平显著增强。表观遗传处理改变了 CT 基因的表达,表明这些基因可能可作为 CC 的生物标志物。强调开展进一步研究以了解和靶向表观遗传机制以改善 CC 治疗的重要性是不过分的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/e544b34fa7f1/pone.0307724.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/25c9a90f96bb/pone.0307724.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/d562185d10c9/pone.0307724.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/bc79e1409cba/pone.0307724.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/e544b34fa7f1/pone.0307724.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/67959dcc49c7/pone.0307724.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/698bf603343b/pone.0307724.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/1e0b884ae182/pone.0307724.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/25c9a90f96bb/pone.0307724.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/d562185d10c9/pone.0307724.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/bc79e1409cba/pone.0307724.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/041a/11361649/e544b34fa7f1/pone.0307724.g007.jpg

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Higher Expression Levels of and in Patients with Colon Cancer: Regulated In Vitro by the Inhibition of Methylation and Histone Deacetylation.结肠癌患者中 和 的表达水平升高:通过抑制甲基化和组蛋白去乙酰化体外调控。
Medicina (Kaunas). 2023 May 20;59(5):988. doi: 10.3390/medicina59050988.
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Evidence of Association between CTLA-4 Gene Polymorphisms and Colorectal Cancers in Saudi Patients.
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Identification of potential biomarkers in cancer testis antigens for glioblastoma.胶质母细胞瘤癌睾丸抗原中潜在生物标志物的鉴定。
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Colorectal Cancer in Saudi Arabia: The Way Forward.沙特阿拉伯的结直肠癌:未来之路。
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