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Circ_0001667 Promotes Adriamycin Resistance and Malignant Progression via Targeting the miR-193a-5p/Rap2A Molecular

Shilin Xu1, Wen Luo1, Mengxin Li1

  • 1Department of Oncology, Xichang People's Hospital, XiChang City, China.

Clinical Breast Cancer
|October 26, 2022
PubMed
Abstract

Insights

Circular RNA circ_0001667 promotes adriamycin resistance and breast cancer progression by sponging miR-193a-5p and upregulating Rap2A. This finding reveals a novel mechanism for circ_0001667 in chemoresistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Chemoresistance limits adriamycin (ADM) efficacy in breast cancer (BC).
  • Circular RNAs (circRNAs) regulate chemoresistance through miRNA/mRNA interactions.
  • Previous studies linked circ_0001667 to ADM resistance via the miR-4458/NCOA3 axis.

Purpose of the Study:

  • To investigate the role of circ_0001667 in ADM resistance in breast cancer.
  • To elucidate the miRNA/mRNA network regulated by circ_0001667.
  • To identify potential therapeutic targets for overcoming ADM resistance.

Main Methods:

  • Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for gene expression analysis.
  • Cell counting kit-8 (CCK-8) assay to determine IC50 values.
  • Cell proliferation, apoptosis, migration, and invasion assays (colony formation, EdU, flow cytometry, Transwell).
  • Western blot for protein analysis, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays for target validation.
  • In vivo xenograft tumor models to assess therapeutic effects.

Main Results:

  • Circ_0001667 was highly expressed in ADM-resistant BC tissues and cells.
  • Circ_0001667 downregulation reduced ADM resistance, inhibited proliferation, migration, and invasion, and repressed tumor growth in vivo.
  • Circ_0001667 acted as a sponge for miR-193a-5p, leading to increased Ras-Related Protein 2a (Rap2A) expression.
  • miR-193a-5p upregulation inhibited chemoresistance and BC progression by downregulating Rap2A.

Conclusions:

  • Circ_0001667 promotes ADM resistance and tumor development in breast cancer.
  • The mechanism involves the miR-193a-5p/Rap2A axis, where circ_0001667 upregulates Rap2A by sponging miR-193a-5p.
  • This study provides a novel regulatory mechanism for circ_0001667 in BC chemoresistance.
Keywords:
Adriamycin resistanceBreast cancerRap2Acirc_0001667miR-193a-5p

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