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miR-30a attenuates drug sensitivity to 5-FU by modulating cell proliferation possibly by downregulating cyclin E2 in

Kenta Kawahara1, Masashi Nagata1, Ryoji Yoshida1

  • 1Department of Oral & Maxillofacial Surgery, Faculty of Life Sciences, Kumamoto University 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.

Biochemistry and Biophysics Reports
|September 30, 2021
PubMed

Insights

MicroRNA-30a (miR-30a) is upregulated in oral squamous cell carcinoma (OSCC) resistant to 5-FU chemotherapy. Upregulated miR-30a decreases sensitivity to 5-FU by targeting CCNE2, suggesting miR-30a as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Oral squamous cell carcinoma (OSCC) often develops resistance to 5-fluorouracil (5-FU) chemotherapy.
  • MicroRNAs (miRNAs) play crucial roles in cancer progression and drug resistance.

Purpose of the Study:

  • To investigate the functional role of miR-30a in 5-FU resistance in OSCC.
  • To elucidate the molecular mechanism by which miR-30a affects 5-FU sensitivity.

Main Methods:

  • Comparison of miRNA expression in 5-FU-resistant and parental OSCC cell lines using miRNA microarray.
  • Overexpression and knockdown of miR-30a in OSCC cells.
  • Cell proliferation assays and cell cycle analysis.
  • Identification of miR-30a targets using DNA microarray and bioinformatics.
  • Validation of miR-30a-target interaction using luciferase reporter assay and siRNA knockdown.

Main Results:

  • miR-30a was significantly upregulated in 5-FU-resistant OSCC cell lines.
  • Overexpression of miR-30a decreased cell proliferation and 5-FU sensitivity, inducing G1 cell cycle arrest.
  • Knockdown of miR-30a reversed these effects.
  • Cyclin E2 (CCNE2) was identified as a direct target of miR-30a.
  • CCNE2 knockdown mimicked the effect of miR-30a overexpression on 5-FU sensitivity.

Conclusions:

  • miR-30a contributes to 5-FU resistance in OSCC by downregulating CCNE2.
  • miR-30a may serve as a predictive biomarker for 5-FU-resistant OSCC.
  • Targeting miR-30a could be a potential therapeutic strategy to overcome 5-FU resistance in OSCC.
Keywords:
Cyclin E2DMEM, Dulbecco’s Modified Eagle’s MediumDrug resistanceFive-fluorouracilHNSCC, Head and neck squamous cell carcinomaOSCC, Oral squamous cell carcinomaOral squamous cell carcinomamiR-30amicroRNA

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