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姜黄素对结直肠癌中铁死亡相关基因的影响:来自计算机模拟和体外研究的见解

Impact of curcumin on ferroptosis-related genes in colorectal cancer: Insights from in-silico and in-vitro studies.

作者信息

Firouzjaei Ali Ahmadizad, Aghaee-Bakhtiari Seyed Hamid, Tafti Ali, Sharifi Kazem, Abadi Mohammad Hassan Jafari Najaf, Rezaei Samaneh, Mohammadi-Yeganeh Samira

机构信息

Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Cell Biochem Funct. 2023 Dec;41(8):1488-1502. doi: 10.1002/cbf.3889. Epub 2023 Nov 28.

DOI:10.1002/cbf.3889
PMID:38014635
Abstract

Colorectal cancer (CRC) is responsible for a significant number of cancer-related fatalities worldwide. Researchers are investigating the therapeutic potential of ferroptosis, a type of iron-dependent controlled cell death, in the context of CRC. Curcumin, a natural compound found in turmeric, exhibits anticancer properties. This study explores the effects of curcumin on genes related to ferroptosis (FRGs) in CRC. To gather CRC data, we used the Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Omnibus (GEO) databases, while FRGs were obtained from the FerrDb database and PubMed. We identified 739 CRC differentially expressed genes (DEGs) in CRC and discovered 39 genes that were common genes between FRGs and CRC DEGs. The DEGs related to ferroptosis were enriched with various biological processes and molecular functions, including the regulation of signal transduction and glucose metabolism. Using the Drug Gene Interaction Database (DGIdb), we predicted drugs targeting CRC-DEGs and identified 17 potential drug targets. Additionally, we identified eight essential proteins related to ferroptosis in CRC, including MYC, IL1B, and SLC1A5. Survival analysis revealed that alterations in gene expression of CDC25A, DDR2, FABP4, IL1B, SNCA, and TFAM were associated with prognosis in CRC patients. In SW480 human CRC cells, treatment with curcumin decreased the expression of MYC, IL1B, and EZH2 mRNA, while simultaneously increasing the expression of SLCA5 and CAV1. The findings of this study suggest that curcumin could regulate FRGs in CRC and have the potential to be utilized as a therapeutic agent for treating CRC.

摘要

结直肠癌(CRC)在全球范围内导致了大量与癌症相关的死亡。研究人员正在研究铁死亡(一种铁依赖性的可控细胞死亡)在结直肠癌背景下的治疗潜力。姜黄素是姜黄中发现的一种天然化合物,具有抗癌特性。本研究探讨了姜黄素对结直肠癌中与铁死亡相关基因(FRGs)的影响。为了收集结直肠癌数据,我们使用了基因表达谱交互分析(GEPIA)和基因表达综合数据库(GEO),而FRGs则从FerrDb数据库和PubMed中获取。我们在结直肠癌中鉴定出739个差异表达基因(DEGs),并发现39个基因是FRGs和结直肠癌DEGs之间的共同基因。与铁死亡相关的DEGs富集了各种生物学过程和分子功能,包括信号转导和葡萄糖代谢的调节。使用药物基因相互作用数据库(DGIdb),我们预测了靶向结直肠癌DEGs的药物,并确定了17个潜在的药物靶点。此外,我们在结直肠癌中鉴定出8种与铁死亡相关的必需蛋白质,包括MYC、IL1B和SLC1A5。生存分析显示,CDC25A、DDR2、FABP4、IL1B、SNCA和TFAM基因表达的改变与结直肠癌患者的预后相关。在SW480人结直肠癌细胞中,姜黄素处理降低了MYC、IL1B和EZH2 mRNA的表达,同时增加了SLCA5和CAV1的表达。本研究结果表明,姜黄素可以调节结直肠癌中的FRGs,有潜力作为治疗结直肠癌的治疗剂。

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