Faculty Collaboration Database

MicroRNA-17 acts as a tumor chemosensitizer by targeting JAB1/CSN5 in triple-negative breast cancer. Cancer Lett 2019 Nov 28;465:12-23

Date

09/02/2019

Pubmed ID

31473252

DOI

10.1016/j.canlet.2019.08.016

Scopus ID

2-s2.0-85071611443 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. Evidence indicates that aberrant JAB1/CSN5 expression is associated with advanced tumor stage and poor prognosis in breast cancer. In this study, we evaluated expression of JAB1 in TNBC and potential mechanisms regulating this expression. We found that miR-17 expression was lower in TNBC than in normal breast tissue, and miR-17 expression in patients with TNBC was associated with a good prognosis. Furthermore, JAB1 expression was regulated by miR-17 in TNBC cells, and mice with miR-17-overexpressing tumors had less tumor growth and lower tumor JAB1 expression than control mice. We also demonstrated that miR-17 suppressed JAB1's oncogenic function, leading to tumor growth inhibition and sensitizing TNBC cells to chemotherapy treatment. JAB1 knockdown in TNBC cells mimicked the effect of miR-17 overexpression and led to significant decreases in cell proliferation, colony formation, and migration, increased p27 expression, and enhanced cisplatin sensitivity. Our findings suggest that miR-17 acts as a tumor suppressor by directly targeting JAB1 in TNBC; this may lead to novel therapeutic targets and strategies for treating TNBC patients.

Author List

Wang S, Oh DY, Leventaki V, Drakos E, Zhang R, Sahin AA, Resetkova E, Edgerton ME, Wu W, Claret FX

MESH terms used to index this publication - Major topics in bold

Animals
COP9 Signalosome Complex
Cell Line, Tumor
Cell Proliferation
Cisplatin
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Humans
Intracellular Signaling Peptides and Proteins
Mice
MicroRNAs
Middle Aged
Peptide Hydrolases
Prognosis
Triple Negative Breast Neoplasms
Up-Regulation
Xenograft Model Antitumor Assays