Unveiling the role of MDH1 in breast cancer drug resistance through single-cell sequencing and schottenol intervention

This study utilizes single-cell RNA sequencing data to reveal the transcriptomic characteristics of breast cancer and normal epithelial cells. Nine significant cell populations were identified through stringent quality control and batch effect correction. Further classification of breast cancer epithelial cells based on the PAM50 method and clinical subtypes highlighted significant heterogeneity between triple-negative breast cancer (TNBC) and non-triple-negative breast cancer (NTNBC). The study also analyzed myeloid cells and tumor-infiltrating lymphocytes (TILs) within the breast cancer immune microenvironment, identifying 14 TIL subpopulations and assessing their proportion variations across different patients. The CellChat tool revealed a complex cellular communication network within the tumor microenvironment, showing notable differences in communication intensity and patterns between TNBC and NTNBC patients. Additionally, the key regulatory role of the senescence-associated gene MDH1 in breast cancer was confirmed, and its impact on drug sensitivity was explored. Finally, it was discovered that the phytosterol Schottenol inhibits breast cancer cell proliferation by downregulating MDH1 expression and enhances sensitivity to paclitaxel. These findings provide new insights into MDH1 as a therapeutic target and suggest Schottenol as a potential strategy to overcome breast cancer drug resistance.