Circ-ITCH regulates triple-negative breast cancer progression through the Wnt/β-catenin pathway.

Abstract

Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the role of circ-ITCH in TNBC and found that circ-ITCH was significantly down-regulated in TNBC tissues and cell lines and closely associated with poor prognosis. We therefore constructed the MDA-MB-231 and BT-549 TNBC cell lines stably expressing circ-ITCH by lentiviral vectors to determine its underlying mechanisms in TNBC progression. Most importantly, over-expression of circ-ITCH remarkably inhibited TNBC proliferation, invasion and metastasis both in vitro and in vivo. Mechanistically, we found that circ-ITCH acts as a sponge for miR-214 and miR-17 to increase expression of its ITCH linear isoform, thereby inactivating Wnt/β-catenin signaling. Our combined results show for the first time that circ-ITCH is a tumor suppressor, a promising prognostic biomarker in TNBC and that its restoration could well be a successful strategy in TNBC.

• Authors: S T Wang, L B Liu, X M Li, Y F Wang, P J Xie, Q Li, R Wang, Q Wei, Y H Kang, R Meng, X H Feng
• Journal: Neoplasma (Neoplasma) Vol. 66 Issue 2 Pg. 232-239 (Mar 05 2019) ISSN: 0028-2685 [Print] Slovakia
• PMID: 30509108 (Publication Type: Journal Article)

Chemical References

• MIRN17 microRNA, human
• MIRN214 microRNA, human
• MicroRNAs
• RNA, Circular
• Repressor Proteins
• RNA
• ITCH protein, human
• Ubiquitin-Protein Ligases

Topics

• Apoptosis
• Cell Line, Tumor
• Humans
• MicroRNAs (genetics)
• RNA (genetics)
• RNA, Circular
• Repressor Proteins (genetics)
• Triple Negative Breast Neoplasms (genetics, pathology)
• Ubiquitin-Protein Ligases (genetics)
• Wnt Signaling Pathway