Cornua cervi degelatinatum inhibits breast cancer stem-like cell properties and metastasis via miR-148a-3p-mediated TGF-β/Smad2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cornua cervi degelatinatum (CCD) is formed by removing the gelatinous substance from deer antlers according to traditional methods. It was first recorded in the Shennong's Classic of Materia Medica and has been included in the Pharmacopoeia of the People's Republic of China. It is commonly used in clinical practice for the treatment of diseases such as cancer and infertility.

AIM OF THE STUDY: This study aims to investigate the impact of CCD aqueous extract on the proliferation and stemness of breast cancer (BC) cells, with an emphasis on its regulation of miR-148a-3p expression and associated molecular pathways.

MATERIALS AND

METHODS

Breast cancer cells were treated with various concentrations of CCD to assess its effects on cancer stem cell (CSC) features, epithelial-mesenchymal transition (EMT) markers, and overall plasticity. The UALCAN platform was utilized to analyze the relationship between miR-148a-3p and Smad2 expression. Functional experiments involving miR-148a-3p overexpression were performed to elucidate CCD's modulatory effects on the TGF-β/Smad2 pathway. Furthermore, molecular docking analysis was conducted to predict the binding affinity of CCD's active components to Smad2.

RESULTS

The CCD aqueous extract significantly reduced BC cell viability in vitro and dose-dependently suppressed the expression of stemness- and EMT-related proteins. Bioinformatics analysis and luciferase reporter assays validated miR-148a-3p as a direct regulator of Smad2, inhibiting the TGF-β/Smad2 signaling pathway. Molecular docking revealed strong binding interactions between CCD's active components and Smad2.

CONCLUSIONS

CCD exhibits anti-BC effects by working synergistically with miR-148a-3p to inhibit the TGF-β/Smad2 pathway, thereby reducing BC stemness and EMT progression. These findings provide valuable insights into the molecular mechanisms underlying CCD's therapeutic potential in BC treatment.