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Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer

Yiran Liang1, Xiaojin Song1, Yaming Li1

  • 1Department of Breast Surgery, Qilu Hospital, Shandong University, Shandong, China.

Molecular Therapy. Nucleic Acids
|July 15, 2019
PubMed

Insights

This study identifies circBMPR2, a circular RNA that is downregulated in breast cancer. Lower circBMPR2 levels promote cancer progression and tamoxifen resistance by sponging miR-553, thus upregulating USP4.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are increasingly recognized for their roles in cancer development.
  • The specific functions of circRNAs in breast cancer progression and treatment resistance are not fully understood.

Purpose of the Study:

  • To identify and characterize novel circRNAs involved in breast cancer.
  • To elucidate the functional role of circBMPR2 in breast cancer metastasis and tamoxifen resistance.

Main Methods:

  • Quantitative real-time PCR to measure circBMPR2 expression in breast cancer tissues and cell lines.
  • Cell proliferation, migration, and invasion assays following circBMPR2 knockdown or overexpression.
  • Western blotting and luciferase reporter assays to investigate the interaction between circBMPR2, miR-553, and USP4.
  • Apoptosis assays to assess tamoxifen sensitivity.

Main Results:

  • circBMPR2 expression was significantly lower in metastatic breast cancer tissues and negatively correlated with cell motility.
  • circBMPR2 knockdown enhanced breast cancer cell proliferation, migration, and invasion.
  • circBMPR2 knockdown promoted tamoxifen resistance by inhibiting apoptosis, while overexpression decreased resistance.
  • circBMPR2 acts as a miR-553 sponge, relieving miR-553's suppression of its target, USP4, a tumor suppressor.

Conclusions:

  • circBMPR2 functions as a tumor suppressor in breast cancer by inhibiting progression and tamoxifen resistance.
  • The circBMPR2/miR-553/USP4 axis represents a potential therapeutic target for breast cancer treatment.
Keywords:
USP4breast cancercircBMPR2miR-553tamoxifen resistancetumor suppressor

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