Overexpression of circZNF720 Inhibits Hepatocellular Carcinoma Progression by Regulating miR-421/MAPK9

Mol Biotechnol. 2024 May;66(5):1165-1173. doi: 10.1007/s12033-023-01016-2. Epub 2023 Dec 30.

Abstract

Hepatocellular carcinoma (HCC) is characterized by high incidence, high death rate and poor long term prognosis. Abnormal expression of circular RNA (circRNA) has been demonstrated to be closely associated with malignant progression of HCC. However, the effect of circZNF720 on HCC is largely incompletely understood. This study sought to explore the effect of circZNF720 on the progression of HCC by CCK-8, transwell, and flow cytometry experiments. The prognosis of circZNF720 on patients was analyzed by Kaplan-Meier curve. Then, the regulatory mechanisms among circZNF720, miR-421, and MAPK9 were identified by qRT-PCR, dual-luciferase reporter assay, and RIP analysis, respectively. The outcomes of this study disclosed that circZNF720 was lowly expressed in HCC, and this low expression was strongly linked with a poor prognosis for HCC patients. Overexpression of circZNF720 inhibited the proliferation, migration, and invasion of cells, and increased the apoptosis of cells. Mechanistic studies revealed that circZNF720 targeted miR-421 and regulated the development of HCC by acting as a sponge for miRNAs. In addition, MAPK9 was a downstream target of miR-421, and circZNF720 introduction hampered HCC progression by upregulating MAPK9 expression through sponging miR-421. In conclusion, circZNF720 restrained HCC progression by targeting miR-421/MAPK9. This study provides a novel target for the treatment of HCC.

Keywords: Hepatocellular Carcinoma; MAPK9; circZNF720; miR-421.

MeSH terms

  • Apoptosis* / genetics
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Prognosis
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism

Substances

  • MicroRNAs
  • RNA, Circular
  • MIRN421 microRNA, human