MicroRNA-203a inhibits breast cancer progression through the PI3K/Akt and Wnt pathways

Sci Rep. 2024 Feb 27;14(1):4715. doi: 10.1038/s41598-024-52940-5.

Abstract

MicroRNA expression in breast cancer (BC) is explored both as a potential biomarker and for therapeutic purposes. Recent studies have revealed that miR-203a-3p is involved in BC, and importantly contributes to BC chemotherapy responses; however, the regulatory pathways of miR-203a in BC remain elusive. Hence, we aimed to investigate the miR-203a regulatory mechanisms and their potential functions in the progress of BC. To this end, the miR-203a potential involving pathways was predicted by databases analyzing its target genes. The relations between miR-203a, the phosphatidylinositol 3'-kinase (PI3K)-Akt, and Wnt signaling pathways were mechanistically investigated. Our results revealed that miR-203a inhibited the activation of the PI3K/Akt and Wnt pathways and reduced its downstream cell cycle signals, including Cyclin D1 and c-Myc. Moreover, the overexpression of miR-203a drastically arrested the cell cycle at subG1 and G1 phases, decreased the viability, proliferation, and migration, and increased apoptosis of BC cells. Therefore, miR-203a-3p may be considered a tumor suppressor factor and a potential biomarker or therapeutic target for BC.

MeSH terms

  • Biomarkers
  • Breast Neoplasms* / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / metabolism
  • Neoplastic Processes
  • Phosphatidylinositol 3-Kinase / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Wnt Signaling Pathway / genetics

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinase
  • Phosphatidylinositol 3-Kinases
  • Biomarkers

Grants and funding