MicroRNA-142-3p chemo-sensitizing breast cancer to docetaxel: apoptosis and cell cycle arrest induction, and migration suppression

Document Type : Original Article

Authors

1 Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran

2 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

3 Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Odense, Denmark

Abstract
Docetaxel (DTX) is widely utilized in breast cancer treatment. However, cancer cell resistance has limited its anti-tumor efficacy. Some molecules called microRNAs (miRNAs), acting like fine-tuned switches, can influence how breast cancer develops and spreads. We conducted a study to examine if augmenting breast cancer cells with a particular molecule, known as miRNA-142-3p, could improve the efficacy of a widely used treatment called DTX. The expression level of miR-142-3p was initially assessed in MDA-MB-468 cells. The miRNA transfection was performed to conduct additional experiments. The impact of a combined treatment involving DTX and miRNA-142-3p on both cell migration (by wound healing assay) and apoptosis (using annexin V/Propidium iodide staining) was examined. Cell viability was determined through the MTT assay, and gene expression was quantified using quantitative real-time polymerase chain reaction. The combined application of DTX and miRNA-142-3p resulted in a significant decrease in the expression of factors promoting tumor growth, such as SOX2, Octamer 4, HMGA2, Kruppel-like factor 4, and Bach-1. Additionally, the combination of miRNA-142-3p and DTX initiated apoptotic cell death. Moreover, the progression of breast cancer cells was impeded by inducing cell cycle arrest at the G1 phase. This combination also efficiently restrained the migration and invasion of breast cancer cells. The DTX or miRNA-142-3p alone can suppress malignant behavior and progression of breast cancer cells, but their combination elicits a synergistic effect that further enhances breast cancer inhibition. In summary, miRNA-142-3p transfection can be administered in conjunction with DTX therapy to enhance its cytotoxicity against breast cancer cells and prevent chemoresistance.

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Subjects


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Volume 15, Issue 11
November 2024
Pages 629-643

  • Receive Date 08 February 2024
  • Revise Date 24 April 2024
  • Accept Date 29 June 2024