Wu Mengqing, Liu Yang, Zhu Xiao, Zhang Xiaoke, Kong Qinghong, Lu Wei, Yuan Xiao, Liu Yunlai, Liu Yang, Lu Keyu, Dai Yangxue, Zhang Bo
College of Basic Medicine, Zunyi Medical University, Zunyi 563000, Guizhou Province, China.
School of Public Health, Zunyi Medical University, Zunyi 563000, Guizhou Province, China.
Int J Biol Macromol. 2025 Jun;311(Pt 4):143555. doi: 10.1016/j.ijbiomac.2025.143555. Epub 2025 Apr 26.
The i-motif, a cytosine-rich DNA structure formed under acidic conditions, plays a pivotal role in regulating gene expression and holds significant therapeutic potential across various diseases. Found in the promoter regions of oncogenes such as Bcl-2, C-MYC, and KRAS, i-motifs dynamically interact with transcription factors and ligands to modulate oncogene activity. Their pH-sensitive nature enables innovative applications, including cellular pH sensors like the "i-switch" and drug delivery platforms such as DNA hydrogels that release therapeutics in acidic tumor microenvironments. However, challenges remain in developing specific ligands and detection methods. Advances in nanotechnology and multi-target therapies highlight the transformative potential of i-motifs in precision medicine. This review underscores the importance of i-motifs as therapeutic targets and tools, bridging fundamental research with clinical applications in oncology, metabolic disorders, and neurodegenerative diseases.
i-基序是一种在酸性条件下形成的富含胞嘧啶的DNA结构，在调节基因表达中起关键作用，在各种疾病中具有巨大的治疗潜力。i-基序存在于Bcl-2、C-MYC和KRAS等癌基因的启动子区域，与转录因子和配体动态相互作用以调节癌基因活性。它们对pH敏感的特性使其具有创新应用，包括像“i-开关”这样的细胞pH传感器以及在酸性肿瘤微环境中释放治疗药物的DNA水凝胶等药物递送平台。然而，在开发特异性配体和检测方法方面仍存在挑战。纳米技术和多靶点疗法的进展凸显了i-基序在精准医学中的变革潜力。本综述强调了i-基序作为治疗靶点和工具的重要性，将基础研究与肿瘤学、代谢紊乱和神经退行性疾病的临床应用联系起来。
