DNA Topoisomerase II-α Regulated by miR-22-5p Promotes Hepatocellular Carcinoma Invasion and Migration through the Hippo Pathway

Oxid Med Cell Longev. 2022 Oct 17:2022:4277254. doi: 10.1155/2022/4277254. eCollection 2022.

Abstract

DNA topoisomerases (TOPs) are dysregulated in various types of cancer. However, how TOP II-alpha (TOP2A) contributes to hepatocellular carcinoma (HCC) progression remains elusive. Cohort analysis revealed that the increased expression of TOP2A was associated with poor clinical outcomes and TOP2A was significantly upregulated in HCC tissues and cell lines. In vitro, TOP2A expression level is related to cell invasion and migration, which may be due to the alteration of epithelial-mesenchymal transition by the TOP2A. Moreover, we used verteporfin (a Hippo inhibitor) to test how the Hippo pathway promotes the effect of TOP2A on the HCC phenotype and found that TOP2A induces tumor progression through the Hippo pathway. Finally, miR-22-5p inhibited tumor progression by sponging TOP2A.

Publication types

  • Retracted Publication

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA Topoisomerases, Type II* / genetics
  • DNA Topoisomerases, Type II* / metabolism
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway / genetics
  • Hippo Signaling Pathway / physiology
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Verteporfin

Substances

  • DNA Topoisomerases, Type II
  • MicroRNAs
  • MIRN22 microRNA, human
  • Verteporfin
  • TOP2A protein, human