Electroacupuncture Combined with Exercise Intervention Regulates the YTHDF1–MAML2–Wnt Axis: A New Strategy to Inhibit Breast Cancer Bone Metastasis

Background Breast cancer is a highly malignant tumor, and the incidence rate of bone metastasis is high. Electroacupuncture (EA) therapy has also shown therapeutic effects in reducing cancer-related symptoms and regulating bone metabolism. However, AE therapy combined with exercise intervention (EA-EX) has not been investigated in breast cancer bone metastasis. Methods The pathological changes in bone tissues were observed through hematoxylin/eosin staining and tartrate-resistant acid phosphatase staining. The protein expressions of genes were tested through Western blot. The N 6 -methyladenosine level was determined through a commercial kit. The interaction between mastermind-like transcriptional coactivator 2 (MAML2) and YTH domain family member 1 (YTHDF1) was examined through RNA immunoprecipitation assay. The fluorescent intensity was verified through luciferase reporter assay. Results EA-EX treatment alleviated breast cancer bone metastasis by reducing bone destruction. Moreover, EA-EX treatment regulated the YTHDF1–MAML2–wingless-related integration site (Wnt) axis. Further experiments revealed that MAML2 promoted osteoclast differentiation. Finally, YTHDF1 was shown to interact with MAML2 and suppress the Wnt/β-catenin signaling pathway. Conclusion These results demonstrate that EA-EX may regulate the YTHDF1–MAML2–Wnt axis, which may provide a new therapeutic strategy for inhibiting breast cancer bone metastasis.