Exploring Specific miRNA-mRNA Axes With Relationship to Taxanes-Resistance in Breast Cancer

Danni Chen1, Chang Bao2,3,4, Feng Zhao1

  • 1Department of Radiation Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Frontiers in Oncology
|September 25, 2020
PubMed

Insights

This study identifies two microRNAs (miRNAs) and three hub genes involved in taxane resistance in breast cancer. These findings offer potential theranostic targets to overcome chemoresistance and improve treatment outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Breast cancer is the most common cancer in women globally.
  • Taxanes are standard chemotherapy, but drug resistance limits efficacy.
  • Understanding resistance mechanisms is crucial for improving breast cancer treatment.

Purpose of the Study:

  • To identify microRNAs (miRNAs) and genes associated with taxane resistance in breast cancer.
  • To elucidate the functional roles of identified miRNAs and genes in chemoresistance.
  • To explore potential theranostic targets for overcoming taxane resistance.

Main Methods:

  • Screening of dysregulated miRNAs in taxane-resistant breast cancer samples.
  • Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes.
  • Dual-luciferase reporter assays to confirm miRNA-target interactions.
  • Validation of gene functions in proliferation and chemoresistance.

Main Results:

  • miR-335-5p and let-7c-5p were identified as key miRNAs in taxane resistance.
  • CXCL9, CCR7, and SOCS1 were identified as hub genes positively related to taxane sensitivity.
  • Direct regulatory relationships between miRNAs and hub genes were confirmed.
  • CXCL9, CCR7, and SOCS1 were validated to regulate proliferation and chemoresistance.

Conclusions:

  • The study highlights the theranostic potential of miR-335-5p/CXCL9 and let-7c-5p/CCR7/SOCS1 axes in taxane-resistant breast cancer.
  • These molecular axes represent novel targets for overcoming chemotherapy resistance.
  • Findings provide insights into the complex mechanisms underlying taxane resistance in breast cancer.

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