<scp>YTHDF3</scp> Mediates the Occurrence and Development of Breast Cancer by Regulating Glycolysis Through the <scp>mTOR</scp> – <scp>HIF1α</scp> – <scp>LHDA</scp> Axis

Breast cancer, a malignant tumour that frightens women, ruthlessly claims the lives of tens of thousands of women around the world every year. However, the mechanism by which YTHDF3 regulates the occurrence and development of breast cancer is still imperfect. In this study, we used bioinformatics to analyse the expression of YTHDF3 in breast cancer and verified it in clinical specimens. In addition, YTHDF3 knockdown breast cancer cell lines were used to determine the biological role of YTHDF3 in breast cancer through functional experiments such as CCK-8 assay, transwell assay, clonal proliferation and cell cycle assay. Lactate analysis, seahorse assay, RT-qPCR and Western blot were used to explore the downstream mechanism of YTHDF3, and rescue experiments were performed with small molecule activators to repeatedly confirm the downstream targets. Finally, YTHDF3 knockout breast cancer cell lines were used to establish cell line-derived xenograft (CDX) mouse models to further confirm the biological function of YTHDF3 in breast cancer and the possible regulatory mechanism. Our results showed that YTHDF3 was highly expressed in breast cancer cells and clinical tissues, and YTHDF3 enhanced the proliferation and migration ability of breast cancer. Mechanistically, YTHDF3 enhances the expression of HIF1α and LDHA and glycolysis by inducing the phosphorylation of mTOR, and finally promotes the occurrence and development of breast cancer. In addition, YTHDF3 can be used as a helpful biomarker in various cancers, including breast cancer. We aimed to elucidate the role of YTHDF3 in breast cancer development and provide evidence for improving the diagnosis and treatment of breast cancer. In this study, we elucidated that YTHDF3 regulates the glycolysis level, proliferation and migration of breast cancer through the mTOR-HIF1α-LDHA axis. Interference of the YTHDF3 expression is a potential target for breast cancer treatment, which provides strong evidence for improving diagnosis and treatment methods.