Bioinformatic and experimental identification of TCMs enhancing miR-708 expression in triple-negative breast cancer

• High miR-708 predicts better prognosis in HR-neg breast cancer, especially TNBC. • Network pharmacology identifies TCM candidates targeting TNBC. • G. uralensis and S. flavescens inhibit TNBC growth and induce apoptosis. • G. uralensis shows pro-apoptotic and anti-tumor potential for TNBC therapy. Breast cancer remains the most prevalent and life-threatening malignancy among women, with triple-negative breast cancer (TNBC) posing a major clinical challenge due to the lack of targeted therapies. Traditional Chinese Medicine (TCM), a comprehensive system of knowledge refined over thousands of years, has gained increasing recognition for its potential in cancer treatment, including TNBC management. Our previous research identified miR-708 as a promising therapeutic target. This study aimed to apply bioinformatic screening to identify potential TCMs that regulate miR-708 expression and inhibit TNBC progression, offering potential for integrating traditional medicine into modern cancer treatment. By using bioinformatic screening with experimental validation, we identified and confirmed that Astragalus membranaceus, Sophora flavescens, Bupleurum chinense , and Glycyrrhiza uralensis effectively induced miR-708 expression and reduced NRAS and Rap1B expression, leading to the inhibited proliferation, anchorage-independent growth ability and induced apoptosis in MDA-MB-231 and HCC1395 TNBC cell lines. Among them, Sophora flavescens and Glycyrrhiza uralensis showed the strongest effects, with Glycyrrhiza uralensis also significantly suppressing cell migration. Taken together, our findings suggest that Glycyrrhiza uralensis may serve as a promising candidate for TNBC treatment, potentially paving the way for novel therapeutic strategies.