MiR-125b regulates epithelial-mesenchymal transition via targeting Sema4C in paclitaxel-resistant breast cancer cells

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• MicroRNAs (miRNAs) are implicated in chemotherapy resistance in breast cancer.
• The precise mechanisms of chemotherapy-induced epithelial-mesenchymal transition (EMT) remain incompletely understood.
• Paclitaxel resistance is a significant clinical challenge in breast cancer treatment.

Purpose of the Study:

• To investigate the role of miR-125b in paclitaxel resistance and EMT in breast cancer cells.
• To elucidate the regulatory pathway involving miR-125b, Sema4C, and EMT in paclitaxel-resistant cells.
• To explore therapeutic strategies targeting miR-125b or Sema4C to overcome chemotherapy resistance.

Main Methods:

• Utilized stable paclitaxel-resistant (PR) breast cancer cell lines (MCF-7 PR, SKBR3 PR).
• Assessed miR-125b expression levels in PR cells compared to sensitive cells.
• Employed miR-125b mimics for ectopic expression and evaluated EMT phenotype reversal.
• Investigated the interaction between miR-125b and its target gene, Sema4C.
• Determined the effect of miR-125b overexpression or Sema4C depletion on paclitaxel sensitivity.

Main Results:

• miR-125b was significantly downregulated in paclitaxel-resistant breast cancer cells.
• Ectopic expression of miR-125b reversed the mesenchymal phenotype associated with EMT in PR cells.
• miR-125b regulated paclitaxel-induced EMT, partly through its target Sema4C.
• Overexpression of miR-125b or depletion of Sema4C sensitized PR cells to paclitaxel treatment.

Conclusions:

• miR-125b plays a critical role in mediating EMT and chemotherapy resistance in breast cancer.
• Targeting the miR-125b/Sema4C axis presents a potential strategy to enhance paclitaxel efficacy.
• Upregulating miR-125b or inhibiting Sema4C may offer novel therapeutic approaches for overcoming breast cancer chemotherapy resistance.