目的:探讨miR‑370‑3p通过靶向WNT7B调控Wnt/β‑catenin信号通路及其对结直肠癌（colorectal cancer，CRC）细胞有氧糖酵解的影响。 方法:采用RT‑qPCR检测CRC及正常组织中miR‑370‑3p的表达，结合数据库分析其与患者预后的相关性。通过双荧光素酶报告实验验证miR‑370‑3p与WNT7B的靶向结合。使用CCK‑8、细胞划痕实验、Transwell和流式细胞术评估miR‑370‑3p对CRC细胞增殖、迁移、侵袭及凋亡的影响，检测葡萄糖利用率、乳酸生成及糖酵解关键因子葡萄糖转运蛋白1（facilitative glucose transporter1，GLUT1）和乳酸脱氢酶A型（lactate dehydrogenase A，LDHA）的表达。通过Western blot检测Wnt/β‑catenin通路相关蛋白（如β‑catenin、TCF‑4、c‑Myc、CyclinD1）的表达，通过免疫共沉淀和免疫荧光观察β‑catenin与丙酮酸激酶M2型（pyruvate kinase M2，PKM2）的结合及其核转位。采用Spearman相关分析方法评估β‑catenin与糖酵解关键因子（GLUT1、LDHA）表达的相关性。 结果:miR‑370‑3p在CRC组织中表达明显低于正常组织，且与患者的年龄、临床分期和淋巴结转移明显相关（P<0.05）。功能实验结果表明，miR‑370‑3p通过靶向WNT7B抑制Wnt/β‑catenin信号通路，明显抑制CRC细胞的增殖、迁移、侵袭及有氧糖酵解，促进细胞凋亡（P<0.01）。进一步研究发现，miR‑370‑3p通过降低β‑catenin的活性，抑制其与PKM2在细胞核中的结合，下调GLUT1和LDHA的表达，从而抑制有氧糖酵解。 结论:miR‑370‑3p通过靶向WNT7B抑制Wnt/β‑catenin信号通路，降低β‑catenin与PKM2的核内结合，下调GLUT1和LDHA的表达，从而抑制CRC细胞的有氧糖酵解和增殖，促进凋亡。本研究为CRC的靶向治疗提供了新的潜在策略。

Objective:To investigate the effects of miR‑370‑3p on aerobic glycolysis in colorectal cancer （CRC） cells by targeting WNT7B and regulating the Wnt/β‑catenin signaling pathway. Methods:RT‑qPCR was used to detect the expression levels of miR‑370‑3p in CRC and normal tissues， and database analysis was performed to assess its correlation with patient prognosis. A dual‑luciferase reporter assay was conducted to verify the direct binding of miR‑370‑3p to WNT7B. The effects of miR‑370‑3p on CRC cell proliferation， migration， invasion， and apoptosis were evaluated using CCK‑8， wound healing assay， Transwell and flow cytometry assays. Glucose utilization， lactate production， and the expression levels of key glycolytic factors， including facilitative glucose transporter 1 （GLUT1） and lactate dehydrogenase A （LDHA） were assessed. Western blot was performed to examine the expression of Wnt/β‑catenin pathway components， including β‑catenin， TCF‑4， c‑Myc， and Cyclin D1. Co‑immunoprecipitation and immunofluorescence assays were used to investigate the interaction between β‑catenin and pyruvate kinase M2 （PKM2） and their nuclear localization. Finally， Spearman correlation analysis was conducted to evaluate the relationship between β‑catenin and key glycolytic factors （GLUT1 and LDHA）. Results:miR‑370‑3p was significantly downregulated in CRC tissues and showed a significant association with patient age， clinical stage， and lymph node metastasis （P<0.05）. Functional experiments demonstrated that miR‑370‑3p inhibited the Wnt/β‑catenin signaling pathway by targeting WNT7B， thereby suppressing CRC cell proliferation， migration， invasion， and aerobic glycolysis while promoting apoptosis （P<0.01）. Further studies revealed that miR‑370‑3p reduced β‑catenin activity， inhibited its nuclear interaction with PKM2， and downregulated GLUT1 and LDHA expression， thereby suppressing aerobic glycolysis. Conclusion:miR-370-3p inhibits the Wnt/β-catenin signaling pathway， reduces the nuclear binding of β-catenin and PKM2 by targeting WNT7B， leads to the downregulation of GLUT1 and LDHA expression， thereby inhibiting aerobic glycolysis and proliferation of CRC cells and promoting apoptosis. These findings provide a potential therapeutic target for CRC treatment.

R735.34

海南省自然科学基金（822QN448，823RC564）；海南省卫生健康行业科研项目（22A200214）