circRNA_0025202 Regulates Tamoxifen Sensitivity and Tumor Progression via Regulating the miR-182-5p/FOXO3a Axis in

Yuting Sang1, Bing Chen2, Xiaojin Song1

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

Insights

Circular RNAs (circRNAs) like hsa_circ_0025202 show promise in overcoming tamoxifen resistance in hormone receptor-positive breast cancer by regulating the miR-182-5p/FOXO3a axis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hormone receptor (HR)-positive breast cancer is commonly treated with tamoxifen.
  • Tamoxifen resistance is a significant clinical challenge, necessitating new therapeutic strategies.
  • Circular RNAs (circRNAs) are emerging as key regulators in cancer development and drug resistance.

Purpose of the Study:

  • To investigate the role of circRNAs in tamoxifen resistance in HR-positive breast cancer.
  • To identify specific circRNAs involved in tamoxifen resistance.
  • To elucidate the molecular mechanisms underlying the function of identified circRNAs.

Main Methods:

  • Established a tamoxifen-resistant MCF-7 cell line and performed RNA sequencing to profile circRNA expression.
  • Selected and validated the expression of hsa_circ_0025202 in clinical specimens.
  • Conducted gain- and loss-of-function assays, bioinformatics analysis, luciferase reporter assays, and in vivo experiments.

Main Results:

  • hsa_circ_0025202 was significantly downregulated in tamoxifen-resistant cells and associated with poorer prognostic factors.
  • hsa_circ_0025202 suppressed cell proliferation, migration, and enhanced tamoxifen sensitivity.
  • hsa_circ_0025202 acts as a miRNA sponge for miR-182-5p, regulating the miR-182-5p/FOXO3a axis.

Conclusions:

  • hsa_circ_0025202 plays an anti-oncogenic role in HR-positive breast cancer.
  • hsa_circ_0025202 can re-sensitize cells to tamoxifen by targeting the miR-182-5p/FOXO3a pathway.
  • hsa_circ_0025202 holds potential as a novel therapeutic marker for tamoxifen-resistant breast cancer.

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