miR-302a/b/c/d cooperatively inhibit BCRP expression to increase drug sensitivity in breast cancer cells

Yan Wang1, Lin Zhao1, Qinghuan Xiao2

  • 1Department of Pharmacology, School of Pharmacy, China Medical University, Puhe Road 77, Shenyang North New Area, Shenyang, 110122, Liaoning Providence, PR China.

Gynecologic Oncology
|December 9, 2015
PubMed
Abstract

Insights

MicroRNA-302S (miR-302S) can reverse drug resistance in breast cancer by targeting BCRP. This microRNA cluster cooperatively downregulates BCRP, enhancing chemosensitivity and tumor growth inhibition.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Genetics

Background:

  • Breast cancer resistance protein (BCRP) is overexpressed in numerous tumors, contributing to multidrug resistance.
  • Understanding the mechanisms of drug resistance is crucial for developing effective breast cancer therapies.

Purpose of the Study:

  • To investigate the role of the microRNA-302S (miR-302S) family in the development of drug resistance in breast cancer.
  • To determine if miR-302S can overcome BCRP-mediated multidrug resistance.

Main Methods:

  • Differential miRNA expression profiling using microarray analysis.
  • Quantitative Real-Time PCR to measure miR-302S family and BCRP mRNA levels.
  • Dual-luciferase reporter assay to confirm targeting of BCRP mRNA by miR-302S.
  • Western blot for BCRP protein levels, MTS assay for cell viability, and flow cytometry for efflux capacity.

Main Results:

  • The miR-302S family was significantly downregulated in mitoxantrone-resistant MCF-7/MX cells overexpressing BCRP.
  • miR-302S directly targeted the 3'-untranslated region of BCRP mRNA, inhibiting its expression.
  • Overexpression of miR-302S increased intracellular drug accumulation, sensitized breast cancer cells to mitoxantrone, and inhibited tumor growth in vivo.

Conclusions:

  • miR-302S inhibits BCRP expression by targeting its mRNA, suggesting a mechanism for overcoming BCRP-mediated chemoresistance.
  • The miR-302S gene cluster may act cooperatively to downregulate BCRP, enhancing chemosensitivity in breast cancer.
  • Targeting the miR-302S gene cluster represents a potential therapeutic strategy for reversing BCRP-mediated chemoresistance in breast cancer.

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