Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Pathol Res Pract. 2024 Oct;262:155533. doi: 10.1016/j.prp.2024.155533. Epub 2024 Aug 11.
Colorectal cancer (CRC) is a major global health concern, with rising incidence and mortality rates. Conventional treatments often come with significant complications, prompting the exploration of natural compounds like curcumin as potential therapeutic agents. Using bioinformatic tools, this study investigated the role of curcumin in CRC treatment. Significant protein interactions between curcumin and target proteins were identified in the STITCH database. Differentially expressed genes (DEGs) associated with CRC were then analyzed from GEO databases. Comparing curcumin targets and CRC-related DEGs, nine significant common targets were identified: DNMT1, PCNA, CCND1, PLAU, MMP3, SOX9, FOXM1, CXCL2, and SERPINB5. Pathway enrichment analyses revealed that curcumin-targeted pathways were primarily related to p53, IL-17, NF-kappa B, TNF, and cell cycle signaling, all crucial in CRC development and progression. Further analyses using DAID and EnrichR algorithms showed that the curcumin targets exhibited greater specificity to bronchial epithelial cells and colorectal adenocarcinoma than other diseases. Analyses via the DSigDB database indicated that curcumin ranks highly among other drugs targeting the identified CRC-related genes. Docking studies revealed favorable binding interactions between curcumin and the key CRC-related proteins, suggesting potential molecular mechanisms by which curcumin may exert its effects. In summary, this study provides bioinformatic and docking evidence that curcumin may exert beneficial effects on CRC by modulating the expression or activity of multiple CRC-susceptibility genes involved in critical signaling pathways. These findings warrant further experimental validation and support the potential of curcumin as a therapeutic agent for CRC.
结直肠癌（CRC）是一个全球性的主要健康问题，其发病率和死亡率呈上升趋势。传统的治疗方法往往伴随着严重的并发症，促使人们探索姜黄素等天然化合物作为潜在的治疗剂。本研究利用生物信息学工具探讨了姜黄素在 CRC 治疗中的作用。在 STITCH 数据库中发现了姜黄素与靶蛋白之间的显著蛋白质相互作用。然后从 GEO 数据库中分析与 CRC 相关的差异表达基因（DEGs）。比较姜黄素靶标和 CRC 相关 DEGs 后，鉴定出 9 个显著的共同靶标：DNMT1、PCNA、CCND1、PLAU、MMP3、SOX9、FOXM1、CXCL2 和 SERPINB5。通路富集分析表明，姜黄素靶向通路主要与 p53、IL-17、NF-kappa B、TNF 和细胞周期信号通路相关，这些通路在 CRC 的发生和发展中至关重要。进一步使用 DAID 和 EnrichR 算法分析表明，与其他疾病相比，姜黄素靶标对支气管上皮细胞和结直肠腺癌具有更高的特异性。通过 DSigDB 数据库的分析表明，姜黄素在针对鉴定出的 CRC 相关基因的药物中排名较高。对接研究显示姜黄素与关键 CRC 相关蛋白之间存在有利的结合相互作用，提示姜黄素可能通过调节参与关键信号通路的多个 CRC 易感性基因的表达或活性发挥作用的潜在分子机制。综上所述，本研究提供了生物信息学和对接证据，表明姜黄素可能通过调节参与关键信号通路的多个 CRC 易感性基因的表达或活性，对 CRC 产生有益影响。这些发现需要进一步的实验验证，并支持姜黄素作为 CRC 治疗剂的潜力。
