Circular RNA ITCH has inhibitory effect on ESCC by suppressing the Wnt/β-catenin pathway

Oncotarget. 2015 Mar 20;6(8):6001-13. doi: 10.18632/oncotarget.3469.

Abstract

Circular RNAs with exonic sequences represent a special form of non-coding RNAs, discovered by analyzing a handful of transcribed genes. It has been observed that circular RNAs function as microRNA sponges. In the present study, we investigated whether the expression of circular RNAs is altered during the development of esophageal squamous cell carcinoma (ESCC). Using a TaqMan-based reverse transcriptase polymerase chain reaction assay, the relationship between cir-ITCH and ESCC was analyzed in a total of 684 ESCC and paired adjacent non-tumor tissue samples from eastern and southern China. We found that cir-ITCH expression was usually low in ESCC compared to the peritumoral tissue. The functional relevance of cir-ITCH was further examined by biochemical assays. As sponge of miR-7, miR-17, and miR-214, cir-ITCH might increase the level of ITCH. ITCH hyper expression promotes ubiquitination and degradation of phosphorylated Dvl2, thereby inhibiting the Wnt/β-catenin pathway. These results indicate that cir-ITCH may have an inhibitory effect on ESCC by regulating the Wnt pathway.

Keywords: ESCC; Wnt/β-catenin pathway; cir-ITCH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / metabolism
  • Cell Proliferation / physiology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / metabolism
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Heterografts
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Phosphorylation
  • RNA / biosynthesis
  • RNA / genetics*
  • RNA, Circular
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Transfection
  • Ubiquitin-Protein Ligases / biosynthesis
  • Ubiquitin-Protein Ligases / genetics*
  • Wnt Signaling Pathway*
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • RNA, Circular
  • Repressor Proteins
  • beta Catenin
  • RNA
  • ITCH protein, human
  • Ubiquitin-Protein Ligases