Open AccessCirc-ITCH regulates triple-negative breast cancer progression through the Wnt/β-catenin pathway
Author(s) -
Wang St,
Liu Lb,
Li Xm,
Yafang Wang,
Pei-Jun Xie,
Li Q,
R Wang,
Wei Qin,
Kang Yh,
Rui Meng,
Feng Xh
Publication year - 2019
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2018_180710n460
Subject(s) - triple negative breast cancer , wnt signaling pathway , cancer research , carcinogenesis , breast cancer , catenin , suppressor , gene knockdown , metastasis , biomarker , cancer , biology , medicine , cell culture , signal transduction , microbiology and biotechnology , biochemistry , genetics
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.