研究动态
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姜黄素通过早期生长反应1(EGR1)对结肠癌细胞衰老的影响及机制。

Effect and mechanism of curcumin on colon cancer cell senescence through early growth response 1 (EGR1).

发表日期:2024 Jul 31
作者: Dan Xu, Linjun Li, Zhaomin Yu
来源: GENES & DEVELOPMENT

摘要:

早期生长反应1(EGR1)的表达水平在结肠癌(CC)组织中升高,并且与结直肠癌的不良预后密切相关。然而,EGR1 作为转录因子 (TF) 在 CC 进展中影响细胞衰老的作用仍然很大程度上未被探索。本研究旨在探讨姜黄素通过调节EGR1对结直肠癌细胞衰老的影响。从公共数据库获取与细胞衰老相关的基因,并利用ChIP-X预测的TF。 R2数据库用于检查基因表达与生存之间的关系。 CC细胞系用质粒转染以实现稳定表达。筛选稳定转染的细胞系,并使用实时荧光定量聚合酶链反应 (RT-qPCR) 和蛋白质印迹 (WB) 分析评估 RNA 和蛋白质表达的变化。通过SA-β-Gal染色测量衰老水平。通过软琼脂和基质胶侵袭测定评估细胞增殖和侵袭能力。分子对接用于预测姜黄素和 EGR1 之间的相互作用。使用双荧光素酶报告基因检测检测基因活性变化。结果表明EGR1在CC组织中过度表达并与不良预后相关。作为转录因子,EGR1 负向调节与细胞衰老相关的端粒酶逆转录酶 (TERT) 和沉默调节蛋白 6 (SIRT6) 基因的表达。敲除EGR1会增加细胞衰老速度并抑制细胞增殖和侵袭。姜黄素抑制EGR1的转录活性,从而促进细胞衰老,抑制肿瘤进展。综上所述,姜黄素抑制TF EGR1的活性,影响靶基因TERT和SIRT6的转录和翻译,从而促进细胞衰老,抑制CC细胞增殖。这些发现为 CC.2024 转化癌症研究的靶向治疗提供了潜在的见解。版权所有。
The expression level of early growth response 1 (EGR1) is elevated in colon cancer (CC) tissues and is closely associated with poor prognosis in colorectal cancer. However, the role of EGR1 as a transcription factor (TF) influencing cell senescence in the progression of CC remains largely unexplored. This study aims to investigate the impact of curcumin on colorectal cancer cell senescence by modulating EGR1.Genes associated with cell senescence were obtained from a public database, and ChIP-X predicted TFs were utilized. The R2 database was employed to examine the relationship between gene expression and survival. CC cell lines were transfected with plasmids to achieve stable expression. Stable transfected cell lines were screened, and changes in RNA and protein expression were assessed using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB) analysis. Senescence levels were measured by SA-β-Gal staining. Cell proliferation and invasion capabilities were evaluated through soft agar and Matrigel invasion assays. Molecular docking was used to predict the interaction between curcumin and EGR1. Gene activity changes were detected using a dual luciferase reporter gene assay.The results indicated that EGR1 was overexpressed in CC tissues and correlated with poor prognosis. As a TF, EGR1 negatively regulated the expression of telomerase reverse transcriptase (TERT) and sirtuin 6 (SIRT6) genes associated with cell senescence. Knocking down EGR1 increased the rate of cell senescence and inhibited cell proliferation and invasion. Curcumin inhibited the transcriptional activity of EGR1, thereby promoting cell senescence and inhibiting tumor progression.In conclusion, curcumin hampers the activity of TF EGR1, affecting the transcription and translation of target genes TERT and SIRT6, thus promoting cell senescence and inhibiting CC cell proliferation. These findings provide potential insights for targeted therapy of CC.2024 Translational Cancer Research. All rights reserved.