Xu Dan, Li Linjun, Yu Zhaomin
Department of Oncology, Maternal and Child Health Hospital of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Oncology, Xinhua Hospital of Hubei University of Chinese Medicine, Wuhan, China.
Transl Cancer Res. 2024 Jul 31;13(7):3251-3261. doi: 10.21037/tcr-24-26. Epub 2024 Jul 26.
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.
早期生长反应1（EGR1）在结肠癌（CC）组织中的表达水平升高，且与结直肠癌的不良预后密切相关。然而，EGR1作为一种转录因子（TF）在CC进展过程中影响细胞衰老的作用在很大程度上仍未得到探索。本研究旨在通过调节EGR1来研究姜黄素对结直肠癌细胞衰老的影响。
从公共数据库中获取与细胞衰老相关的基因，并利用ChIP-X预测的转录因子。使用R2数据库检查基因表达与生存之间的关系。用质粒转染CC细胞系以实现稳定表达。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）和蛋白质免疫印迹（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试验评估细胞增殖和侵袭能力。使用分子对接预测姜黄素与EGR1之间的相互作用。使用双荧光素酶报告基因检测法检测基因活性变化。
结果表明，EGR1在CC组织中过表达，且与不良预后相关。作为一种转录因子，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。敲低EGR1可提高细胞衰老率，并抑制细胞增殖和侵袭。姜黄素抑制EGR1的转录活性，从而促进细胞衰老并抑制肿瘤进展。
总之，姜黄素阻碍转录因子EGR1的活性，影响靶基因TERT和SIRT6的转录和翻译，从而促进细胞衰老并抑制CC细胞增殖。这些发现为CC的靶向治疗提供了潜在的见解。
