CircRNA circ-ITCH suppresses papillary thyroid cancer progression through miR-22-3p/CBL/β-catenin pathway

Biochem Biophys Res Commun. 2018 Sep 26;504(1):283-288. doi: 10.1016/j.bbrc.2018.08.175. Epub 2018 Sep 4.

Abstract

While recent evidence has uncovered that circular RNAs (circRNAs) are vital regulators of carcinogenesis, their role in papillary thyroid cancer (PTC) is not clearly understood. In this study, we reveal that lower levels of circRNA circ-ITCH are expressed in PTC tissues than in normal adjacent tissues. Gain-of-functional assays show that circ-ITCH overexpression suppresses PTC cell proliferation and invasion and promotes apoptosis in vitro. Overexpression of circ-ITCH also leads to impaired tumor growth in vivo. Bioinformatics analysis and luciferase reporter assays demonstrate that circ-ITCH sponges miR-22-3p to upregulate the expression of CBL, an E3 ligase of nuclear β-catenin. Elevated levels of CBL suppress activation of the Wnt/β-catenin pathway and consequently attenuates PTC progression. In summary, our study reveals a novel signaling pathway of circ-ITCH/miR-22-3p/CBL/β-catenin involved in PTC development and progression.

Keywords: Circ-ITCH; Circular RNA; Papillary thyroid cancer; Progression.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Computational Biology
  • Disease Progression
  • Female
  • Humans
  • Lentivirus
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-cbl / metabolism*
  • RNA, Untranslated / metabolism*
  • Signal Transduction
  • Thyroid Cancer, Papillary / genetics*
  • Thyroid Cancer, Papillary / metabolism*
  • Thyroid Cancer, Papillary / pathology
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, human
  • MIRN22 microRNA, human
  • MicroRNAs
  • RNA, Untranslated
  • beta Catenin
  • cir-ITCH noncoding RNA, human
  • Proto-Oncogene Proteins c-cbl
  • CBL protein, human