ciRS-7 Enhances the Progression of Hepatocellular Carcinoma through miR-944/NOX4 Pathway

Crit Rev Eukaryot Gene Expr. 2022;32(7):11-24. doi: 10.1615/CritRevEukaryotGeneExpr.2022039225.

Abstract

Recently, increasing numbers of non-coding RNA have been uncovered in research. As a new class of non-coding RNA, circular RNA has been identified to be involved in various diseases including many cancers. The circular RNA ciRS-7 is reported to play critical roles in tumorigenesis. However, the role of ciRS-7 in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression and function of ciRS-7 in HCC cells and cancer tissues. CCK8 was applied to detect the influence of ciRS-7 on proliferation. Wound heal assay and invasion assay were used to identify the effects on migration and invasion. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, RNA pull-down, and luciferase reporter assay were used to investigate the downstream targets of ciRS-7. The results showed that ciRS-7 was highly expressed in both hepatocellular carcinoma cells and tissues. Overexpression of ciRS-7 could promote the proliferation, migration, and invasion of HCC. Further study showed that ciRS-7 regulated the miR-944 level through acting as a microRNA sponge. q-RT-PCR, Western blot, RNA pull-down and dual luciferase activity assays showed that miR-944 targeted and regulated the expression of NOX4. Furthermore, the tumor-promoting effect of ciRS-7 could be blocked by inhibition of miR-944/NOX4. Our study demonstrated that ciRS-7 enhanced the proliferation, migration, and invasion of HCC through miR-944/NOX4 pathway. ciRS-7 could be a promising therapeutic target for HCC.

MeSH terms

  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NADPH Oxidase 4 / genetics
  • NADPH Oxidase 4 / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • RNA, Circular
  • RNA, Long Noncoding* / genetics

Substances

  • MIRN-944 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • RNA, Long Noncoding
  • NADPH Oxidase 4
  • NOX4 protein, human