Evaluation of the impact of miR-3143 on the PI3K/AKT signaling pathway and its subsequent influence on the metastatic phenotype of triple-negative breast cancer cells

Exp Cell Res. 2025 May 1;448(1):114552. doi: 10.1016/j.yexcr.2025.114552. Epub 2025 Apr 9.

Abstract

MicroRNAs (miRNAs) are recognized to have a pivotal role in the progression and metastatic dissemination encompassing diverse cancer varieties, such as triple-negative breast cancer (TNBC). Recent evidence has suggested that specific miRNA species can directly or indirectly influence the onset, progression, and relapse of TNBC. Previous studies have reported the frequent reduction of miR-3143 in TNBC, which appears to coincide with the activation of proliferative signaling pathways. However, the potential restorative effects of miR-3143 on TNBC cellular behavior remain unexplored. In the present study, we utilized exosome-mediated delivery to introduce miR-3143 into TNBC cells and investigated its impact on the PI3K/AKT pathway and the resulting effects on cellular proliferation, movement, and apoptosis. MDA-MB-231 TNBC cells underwent treatment with miR-3143-electroporated human umbilical cord mesenchymal stem cell (HUCMSC)-derived exosomes. RT-qPCR analysis was utilized to assess the influence of miR-3143 overexpression on the expression of its target genes, PIK3CA and AKT1, which was further validated through dual-luciferase reporter assays. Our results demonstrated that the overexpression of miR-3143 could effectively decline the level of AKT1 and PIK3CA by directly binding to their 3'-UTRs. Furthermore, the introduction of miR-3143 into TNBC cells resulted in a significant enhancement of apoptotic activities. Interestingly, the delivery of miR-3143 via HUCMSC-derived exosomes could inhibit the protumorigenic and prometastatic behaviors of TNBC cells, potentially limiting their malignant progression. Collectively, these findings enhance comprehension of the regulatory mechanisms by which miR-3143 can modulate the metastatic potential of TNBC cells. The insights gained from this study may facilitate the creation of innovative miRNA-targeting approaches to combat the aggressive nature of TNBC andstrengthen treatment effectiveness.

Keywords: AKT1; Exosomes; Human umbilical cord mesenchymal stem cells; Metastasis; PIK3CA; Triple-negative breast cancer; miR-3143.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Class I Phosphatidylinositol 3-Kinases / metabolism
  • Exosomes / genetics
  • Exosomes / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Metastasis
  • Phenotype
  • Phosphatidylinositol 3-Kinases* / genetics
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / genetics
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / genetics
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / metabolism
  • Triple Negative Breast Neoplasms* / pathology

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • AKT1 protein, human