Zhu Yiling, Zhang Jiayi, Zhao Xu, Guo Mengmeng, Chen Chao, Zhou Ya, Xu Lin
Key Laboratory of Cancer Prevention and Treatment of Guizhou province, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Guizhou 563000, China.
Key Laboratory of Cancer Prevention and Treatment of Guizhou province, Zunyi, Guizhou 563000, China; Department of Immunology, Zunyi Medical University, Guizhou 563000, China.
Pharmacol Res. 2025 Aug;218:107822. doi: 10.1016/j.phrs.2025.107822. Epub 2025 Jun 13.
Aberrant glycolysis is a hallmark of tumor and a key oncogenic driver. However, the complex regulatory networks and dynamic signaling interactions governing glycolysis within the tumor microenvironment (TME) remain incompletely understood, posing significant challenges for developing targeted metabolic therapies. MicroRNA-7 (miR-7), a highly conserved non-coding RNA, is broadly expressed across tissues and plays pivotal roles in development, immune regulation, and disease pathogenesis, including tumor. Recent evidence positions miR-7 as a multifaceted regulator of tumor glycolysis, capable of modulating glucose metabolism through diverse mechanisms. miR-7 inhibits glucose uptake and glycolytic flux in tumor cells by directly targeting glucose transporters and glycolytic enzymes. Additionally, it influences key signaling pathways that govern the expression of glycolysis-related genes. Notably, miR-7 regulates the HIF-1α/ENO2 axis and impacts immune checkpoint expression, such as PD-L1, thereby reshaping the immunosuppressive TME and facilitating metabolic-immune crosstalk. These findings underscore the unique role of miR-7 in tumor metabolic regulation and its potential as a therapeutic target. This review provides a comprehensive overview of the molecular mechanisms by which miR-7 modulates tumor glycolysis, offering new insights into tumorigenesis and informing the development of precision oncology strategies. We also highlight unresolved questions and future directions, including the potential of miR-7-based combinatorial approaches targeting metabolic and immune pathways in tumor.
异常糖酵解是肿瘤的一个标志，也是关键的致癌驱动因素。然而，肿瘤微环境（TME）中控制糖酵解的复杂调控网络和动态信号相互作用仍未完全了解，这给开发靶向代谢疗法带来了重大挑战。MicroRNA-7（miR-7）是一种高度保守的非编码RNA，在各组织中广泛表达，在发育、免疫调节和包括肿瘤在内的疾病发病机制中发挥关键作用。最近的证据表明，miR-7是肿瘤糖酵解的多方面调节因子，能够通过多种机制调节葡萄糖代谢。miR-7通过直接靶向葡萄糖转运蛋白和糖酵解酶来抑制肿瘤细胞中的葡萄糖摄取和糖酵解通量。此外，它还影响控制糖酵解相关基因表达的关键信号通路。值得注意的是，miR-7调节HIF-1α/ENO2轴并影响免疫检查点的表达，如PD-L1，从而重塑免疫抑制性TME并促进代谢-免疫串扰。这些发现强调了miR-7在肿瘤代谢调节中的独特作用及其作为治疗靶点的潜力。本综述全面概述了miR-7调节肿瘤糖酵解的分子机制，为肿瘤发生提供了新的见解，并为精准肿瘤学策略的发展提供了依据。我们还强调了未解决的问题和未来的方向，包括基于miR-7的联合方法靶向肿瘤代谢和免疫途径的潜力。
