miR-127-3p Inhibits Cell Stemness and Docetaxel Resistance in Triple-Negative Breast Cancer by Targeting KIF3B

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Triple-negative breast cancer (TNBC) exhibits high stemness and docetaxel (DTX) resistance.
• MicroRNAs play crucial roles in cancer progression and drug resistance.
• Understanding the regulatory mechanisms of TNBC stemness and DTX resistance is critical for developing effective therapies.

Purpose of the Study:

• To investigate the role of miR-127-3p in regulating tumor cell stemness and docetaxel resistance in triple-negative breast cancer.
• To identify the downstream target of miR-127-3p involved in these processes.
• To evaluate the therapeutic potential of miR-127-3p in TNBC.

Main Methods:

• Bioinformatic prediction and experimental validation of hsa-miR-127-3p and KIF3B expression in TNBC tissues.
• Kaplan-Meier survival analysis to assess the correlation between miR-127-3p and patient survival.
• In vitro assays to evaluate cell viability, proliferation, migration, invasion, drug resistance, and apoptosis in DTX-resistant TNBC cell lines after miR-127-3p modulation.
• Dual-luciferase reporter assay to confirm the direct binding of miR-127-3p to KIF3B.
• In vivo studies using TNBC nude mouse models to assess the effect of miR-127-3p on tumor growth.

Main Results:

• miR-127-3p was significantly downregulated in TNBC tissues and associated with shorter patient survival.
• Upregulation of miR-127-3p suppressed TNBC cell stemness, reduced docetaxel resistance, and inhibited proliferation, migration, and invasion.
• KIF3B was identified as a direct target of miR-127-3p, and its overexpression reversed the effects of miR-127-3p.
• miR-127-3p inhibited the growth of transplanted tumors in vivo.

Conclusions:

• miR-127-3p acts as a tumor suppressor in TNBC by targeting KIF3B.
• Restoring miR-127-3p levels can reduce TNBC cell stemness and overcome docetaxel resistance.
• miR-127-3p holds promise as a therapeutic agent for enhancing docetaxel efficacy in TNBC treatment.