MicroRNA-424-5p enhances chemosensitivity of breast cancer cells to Taxol and regulates cell cycle, apoptosis, and proliferation

Mol Biol Rep. 2021 Feb;48(2):1345-1357. doi: 10.1007/s11033-021-06193-4. Epub 2021 Feb 8.

Abstract

Combination therapy has been considered as a potential method to overcome the BC chemoresistance. MicroRNAs (miRs) have been suggested as a therapeutic factor in the combination therapy of BC. This project aimed at examining the possible activity and molecular function of miR-424-5p and Taxol combination in the human BC cell line. MDA-MB-231 cells were treated with miR-424-5p mimics and Taxol, in a combined manner or separately. We used the MTT test for assessing the cell proliferation. In addition, flow-cytometry was used for evaluating apoptosis and cell-cycle. Expression levels of underlying molecular factors of miR-424-5p were assessed using western-blotting and qRT-PCR. The obtained results demonstrated that miR-424-5p repressed BC cell proliferation and sensitized these cells to Taxol treatment through the induction of apoptosis. Further investigations showed that miR-424-5p might increase BC chemosensitivity through the regulation of apoptosis-related factors including P53, Caspase-3, Bcl-2, and Bax as well as the proliferation-related gene c-Myc. Moreover, miR-424-5p restoration in combination with Taxol treatment decreased the colony formation by regulating Oct-4 and led to G2 arrest via modulating Cdk-2 expression. Western-blotting demonstrated that miR-424-5p may perform its anti-chemoresistance role by regulating the PD-L1 expression and controlling PTEN/PI3K/AKT/mTOR. Overall, the upregulation of miR-424-5p was indicated to upregulate the sensitivity of BC cells to treatment with Taxol. MiR-424-5p might regulate the chemosensitivity of the BC cell line by modulating PD-L1 and controlling the PTEN/mTOR axis. Therefore, the combination of miR-424-5p with Taxol would represent a novel procedure to treat against BC.

Keywords: Breast cancer; Chemoresistance; MiR-424-5p; Signaling pathway; Taxol.

MeSH terms

  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Caspase 3 / genetics
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / genetics*
  • PTEN Phosphohydrolase / genetics
  • Paclitaxel / pharmacology*
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / genetics

Substances

  • BCL2 protein, human
  • MIRN424 microrna, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-bcl-2
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • CASP3 protein, human
  • Caspase 3
  • Paclitaxel