A frequent somatic mutation in the 3'UTR of GAPDH facilitates the development of ovarian cancer by creating a miR‑125b binding site

Oncol Rep. 2020 Sep;44(3):887-896. doi: 10.3892/or.2020.7663. Epub 2020 Jun 25.

Abstract

Ovarian cancer (OVCA) is one of the most common types of cancer in women worldwide. Recent studies have focused on the presence and effect of somatic mutations in patients with OVCA; however, studies on the roles of mutations located in the untranslated regions (UTR) of genes in OVCA remain limited. In the present study, a frequent somatic mutation in the glyceraldehyde 3‑phosphate dehydrogenase (GADPH) 3'UTR was identified using transcriptome sequencing of 120 pairs of OVCA tissue samples. The mutant GAPDH 3'UTR promoted tumor growth and cell motility. Furthermore, the mutation in the GAPDH 3'UTR significantly downregulated the levels of mature miR‑125b by creating a new miR‑125b binding site. Finally, STAT3 levels were increased in SKOV3 cells stably expressing the mutant GADPH 3'UTR, which is a critical target gene of miR‑125b. In conclusion, the present study demonstrated that the mutation located in GAPDH 3'UTR promoted OVCA growth and development by sponging miR‑125b and thereby affecting STAT3 expression levels.

Keywords: GAPDH; somatic mutation; 3'untranslated region; ovarian cancer; miR‑125b.

Publication types

  • Observational Study

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adult
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Binding Sites / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cytoreduction Surgical Procedures
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / genetics*
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / metabolism
  • Humans
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Middle Aged
  • Mutation
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery
  • Ovary / pathology
  • Ovary / surgery
  • STAT3 Transcription Factor / genetics*
  • Young Adult

Substances

  • 3' Untranslated Regions
  • AGO2 protein, human
  • Argonaute Proteins
  • MIRN125 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • GAPDH protein, human
  • Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)