miRNA-574-5p downregulates ZNF70 and influences the progression of human esophageal squamous cell carcinoma through reactive oxygen species generation and MAPK pathway activation

Anticancer Drugs. 2020 Mar;31(3):282-291. doi: 10.1097/CAD.0000000000000833.

Abstract

There is growing evidence shown that microRNAs (miRNAs) are associated with cancer and can play a role in human cancers as oncogenes or tumor suppressor genes. miRNA-574-5p is a candidate oncogene in various types of cancer, but little is known about biological functions of miR-574-5p in esophageal squamous cell carcinoma (ESCC). In this study, we observe that the expression of miR-574-5p is not only increased in human ESCC tissues but also remarkably increased in cell lines correlates with ZNF70. In vitro, we explored the role of miR-574-5p in ESCC progression via transfection of the miR-574-5p inhibitor into ECA-109 cells. The results show miR-574-5p serve as a tumor promoter regulating cells proliferation and apoptosis in ESCC through mitochondrial-mediated reactive oxygen species (ROS) generation and MAPK pathways. Furthermore, ZNF70 has been proved to as a functional target for miR-574-5p to regulate cells poliferation and apoptosis. In summary, these results suggest that miR-574-5p serves as tumor promoter to promote proliferation and inhibit apoptosis of ESCC cells by targeting ZNF70 via mitochondrial-mediated ROS generation and MAPK pathways. The miR-574-5p/ZNF70 pathway provides a new insight into the molecular mechanisms that the occurrence and development of ESCC and it provides a novel therapeutic target for ESCC.

MeSH terms

  • Apoptosis
  • Disease Progression
  • Down-Regulation
  • Esophageal Neoplasms / etiology*
  • Esophageal Neoplasms / metabolism
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma / etiology*
  • Esophageal Squamous Cell Carcinoma / metabolism
  • Esophageal Squamous Cell Carcinoma / pathology
  • Humans
  • MAP Kinase Signaling System / physiology*
  • Membrane Potential, Mitochondrial
  • MicroRNAs / physiology*
  • Mitochondria / physiology
  • Reactive Oxygen Species / metabolism*
  • Transcription Factors / physiology*
  • Zinc Fingers*

Substances

  • MIRN574 microRNA, human
  • MicroRNAs
  • Reactive Oxygen Species
  • Transcription Factors