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

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.

• Authors: Minnan Wang, Bo Chen, Zixuan Ru, Li Cong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 504 Issue 1 Pg. 283-288 (09 26 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 30190130 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

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

Topics

• 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, metabolism, pathology)
• beta Catenin (metabolism)