肿瘤抑制基因(TSGs)在结肠癌中普遍下调，并通过影响基因组完整性、细胞周期和细胞增殖，在肿瘤发生和癌症进展过程中发挥负面作用。姜黄素(CUR)是一种从中国草药中提取的植物化合物，在结肠癌中具有抗肿瘤作用。然而，CUR是否通过重新激活结肠癌中的TSGs发挥其抗肿瘤作用仍不清楚。在这里，我们通过细胞计数试剂盒、集落形成和伤口愈合实验，证明CUR抑制HT29和HCT116的增殖和迁移。此外，对HCT116细胞进行的mRNA测序的全面生物信息学分析发现，有3505个基因在CUR处理后明显上调。基因本体和Kyoto基因与基因组百科全书分析显示，最上调的基因富集在包含37个TSGs的癌症通路中。随机选择了其中的五个(TSGs)（ARHGEF12、APAF1、VHL、CEBPA和CASP8），进行实时荧光聚合酶链反应验证，结果显示这五个基因在CUR处理后明显重新激活，表明TSGs与CUR介导的结肠癌抑制相关。ARHGEF12是新发现的TSGs，在结肠癌中是一个潜在的治疗靶点。此外，进行了分子对接实验，预测了CUR和ARHGEF12的结合位点，这表明CUR可以通过抑制ARHGEF12和RhoA的结合，阻止结肠癌细胞的侵袭和转移。总之，本研究揭示了CUR通过重新激活TSGs抑制结肠癌细胞的增殖和迁移，为结肠癌治疗提供了新的机制和潜在靶点。© 2023 Wu, Fu, Liu, Zhao, Li, Liu and Liang版权所有

Tumor suppressor genes (TSGs) are commonly downregulated in colon cancer and play a negative role in tumorigenesis and cancer progression by affecting genomic integrity, the cell cycle, and cell proliferation. Curcumin (CUR), a Chinese herb-derived phytochemical, exerts antitumor effects on colon cancer. However, it remains unclear whether CUR exerts its antitumor effects by reactivating TSGs in colon cancer. Here, we demonstrated that CUR inhibited HT29 and HCT116 proliferation and migration by cell-counting kit-8, colony-formation, and wound-healing assays. Furthermore, the comprehensive bioinformatics analysis of mRNA sequencing revealed that 3,505 genes were significantly upregulated in response to CUR in HCT116 cells. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses showed that the most upregulated genes were enriched in cancer pathways containing 37 TSGs. Five (ARHGEF12, APAF1, VHL, CEBPA, and CASP8) of the 37 upregulated TSGs were randomly selected for real-time fluorescence polymerase chain reaction and the verification results showed that these five genes were significantly reactivated after CUR treatment, suggesting that TSGs are related to CUR-mediated colon cancer inhibition. ARHGEF12 is a newly identified TSG and a potential therapeutic target for colon cancer. Furthermore, molecular docking was performed to predict the binding sites of CUR and ARHGEF12, suggesting that CUR can prevent colon cancer cell invasion and metastasis by inhibiting ARHGEF12 and RhoA binding. In conclusion, the present study reveals that CUR inhibits colon cancer cell proliferation and migration by reactivating TSGs, revealing a new mechanism and potential target for colon cancer treatment.Copyright © 2023 Wu, Fu, Liu, Zhao, Li, Liu and Liang.