MicroRNA-10a-5p-mediated downregulation of GATA6 inhibits tumor progression in ovarian cancer

Hum Cell. 2024 Jan;37(1):271-284. doi: 10.1007/s13577-023-00987-3. Epub 2023 Sep 28.

Abstract

Ovarian cancer is the common cause of cancer-related death in women and is considered the most deadly gynecological cancer. It has been established that GATA-binding protein 6 (GATA6) is abnormally expressed in several types of malignant tumors and acts as an oncogenic protein or a tumor suppressor. However, the underlying mechanism of GATA6 in ovarian cancer progression has not been elucidated. Data in the present study revealed that GATA6 expression was negatively correlated to microRNA-10a-5p (miR-10a-5p) in ovarian cancer tissue and cells and that GATA6 is directly targeted by miR-10a-5p. Notably, upregulated miR-10a-5p dramatically inhibited ovarian cancer cell proliferation, tumorigenic ability, migration, and invasion by targeting GATA6. In vitro and in vivo experiments confirmed that miR-10a-5p-mediated downregulation of GATA6 suppressed Akt pathway activation. Overall, our findings suggest that miR-10a-5p could be a novel therapeutic target for ovarian cancer, and targeting the miR-10a-5p/GATA6/Akt axis could improve outcomes in this patient population.

Keywords: Cell proliferation; Epithelial–mesenchymal transition; GATA6 transcription factor; MicroRNA-10a-5p; Ovarian cancer.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • GATA6 Transcription Factor* / antagonists & inhibitors
  • GATA6 Transcription Factor* / genetics
  • Genetic Vectors
  • HEK293 Cells
  • Humans
  • Lentivirus
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • Ovarian Neoplasms* / therapy
  • Xenograft Model Antitumor Assays

Substances

  • GATA6 protein, human
  • GATA6 Transcription Factor
  • MIRN10 microRNA, human
  • MicroRNAs