ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance

Int J Mol Sci. 2022 Jun 16;23(12):6702. doi: 10.3390/ijms23126702.

Abstract

The diverse repertoires of cellular mechanisms that progress certain cancer types are being uncovered by recent research and leading to more effective treatment options. Ovarian cancer (OC) is among the most difficult cancers to treat. OC has limited treatment options, especially for patients diagnosed with late-stage OC. The dysregulation of miRNAs in OC plays a significant role in tumorigenesis through the alteration of a multitude of molecular processes. The development of OC can also be due to the utilization of endogenously derived reactive oxygen species (ROS) by activating signaling pathways such as PI3K/AKT and MAPK. Both miRNAs and ROS are involved in regulating OC angiogenesis through mediating multiple angiogenic factors such as hypoxia-induced factor (HIF-1) and vascular endothelial growth factor (VEGF). The NAPDH oxidase subunit NOX4 plays an important role in inducing endogenous ROS production in OC. This review will discuss several important miRNAs, NOX4, and ROS, which contribute to therapeutic resistance in OC, highlighting the effective therapeutic potential of OC through these mechanisms.

Keywords: HER3; HIF1-α; NOX4; ROS; VEGF; angiogenesis; miRNA dysregulation; ovarian cancer; therapeutic resistance.

Publication types

  • Review

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs* / genetics
  • NADPH Oxidases / metabolism
  • Neovascularization, Pathologic / genetics
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Phosphatidylinositol 3-Kinases
  • Reactive Oxygen Species / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MicroRNAs
  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A
  • NADPH Oxidases