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

作者：Shuang Wang, Lu Liu, X. M. Li, Y. -F. Wang, Peijun Xie, Qiao Li, Ruikang K. Wang, Q. Wei, Yeon-Ho Kang, Rui Meng, Xing Feng · 发表于：Neoplasma · 年份：2018 · DOI：10.4149/neo_2018_180710n460 · 被引用次数：117 · 研究领域：Circular RNAs in diseases、MicroRNA in disease regulation、RNA Research and Splicing

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.