EPAS1 targeting by miR-152-3p in Paclitaxel-resistant Breast Cancer

Area of Science:

• Molecular Biology
• Oncology
• Biochemistry

Background:

• Paclitaxel is crucial for breast cancer chemotherapy, but drug resistance remains a significant challenge.
• MicroRNA-152-3p (miR-152-3p) is implicated in tamoxifen resistance; its role in paclitaxel resistance is unexplored.

Purpose of the Study:

• To investigate the role of miR-152-3p in paclitaxel resistance in breast cancer.
• To identify and validate the target gene of miR-152-3p involved in this resistance mechanism.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) to assess miR-152-3p expression in breast cancer tissues and cells.
• Cell viability (MTT assay) and apoptosis (flow cytometry) analyses in paclitaxel-resistant MCF-7/TAX cells transfected with miR-152-3p mimics.
• Bioinformatics analysis and dual-luciferase reporter assays to identify and confirm EPAS1 as the miR-152-3p target.
• RNA interference (siRNA) to investigate the functional role of EPAS1 in paclitaxel resistance.

Main Results:

• miR-152-3p expression was significantly lower in breast cancer tissues and cells compared to normal controls.
• Overexpression of miR-152-3p in MCF-7/TAX cells reduced cell survival, increased apoptosis, and enhanced sensitivity to paclitaxel.
• Endothelial PAS domain-containing protein 1 (EPAS1) was confirmed as a direct target gene negatively regulated by miR-152-3p.
• Silencing EPAS1 expression mimicked the effects of miR-152-3p overexpression, increasing paclitaxel sensitivity and apoptosis.

Conclusions:

• miR-152-3p enhances breast cancer cell sensitivity to paclitaxel by targeting and downregulating EPAS1 expression.
• This mechanism involves inhibiting cell survival and promoting apoptosis in paclitaxel-resistant cells.
• miR-152-3p represents a potential therapeutic target for overcoming paclitaxel resistance in breast cancer.