Circ_0000775 promotes the migration, invasion and EMT of hepatic carcinoma cells by recruiting IGF2BP2 to stabilize CDC27

Pathol Res Pract. 2022 Jul:235:153908. doi: 10.1016/j.prp.2022.153908. Epub 2022 Apr 22.

Abstract

Background: Hepatic carcinoma (HC) is one of the leading causes of cancer-related death, and the incidence keeps high in the world. The vital role of circular RNAs (circRNAs) in HC development has been revealed to some extent. Circ_0000775, a novel circRNA, has never been thoroughly studied regarding HC.

Methods: Online datasets were utilized to obtain expression pattern of genes in tumor tissues. RT-qPCR and western blot examined the RNA and protein levels of indicated genes. ChIP, DNA pull down, RNA pull down, RIP and luciferase reporter assays were carried out to verify correlation between different factors. Supported by RT-qPCR and western blot analyses, transwell and wound healing assay were implemented for detecting cell migration and invasion and EMT. Additionally, cell EMT was also evaluated via cell morphology observation for calculation of spindle cell number.

Results: High expression of circ_0000775 in HC cells was induced by transcriptionally stimulation by TCF7L2. Circ_0000775 in cytoplasm recruited IGF2BP2 to enhance the mRNA stability of CDC27, thus positively modulating CDC27 expression. Circ_0000775 exacerbated HC cell migration, invasion and EMT through CDC27.

Conclusion: TCF7L2 promoted the transcription of circ_0000775, and circ_0000775 recruited IGF2BP2 to maintain CDC27 mRNA stability, thereby facilitating HC cell migration, invasion and EMT.

Keywords: CDC27; Circ_0000775; Hepatic carcinoma; IGF2BP2; TCF7L2.

MeSH terms

  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome* / genetics
  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome* / metabolism
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / metabolism
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplastic Processes
  • RNA, Circular* / genetics
  • RNA, Circular* / metabolism
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome
  • CDC27 protein, human
  • IGF2BP2 protein, human
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins