Authors
Hanyang Lin, Katharina Rothe, Min Chen, Andrew Wu, Artem Babaian, Ryan Yen, Jonathan Zeng, Jens Ruschmann, Oleh I Petriv, Kieran O'Neill, Tobias Maetzig, David JHF Knapp, Naoto Nakamichi, Ryan Brinkman, Inanc Birol, Donna L Forrest, Carl Hansen, R Keith Humphries, Connie J Eaves, Xiaoyan Jiang
Publication date
2020/7/30
Journal
Blood, The Journal of the American Society of Hematology
Volume
136
Issue
5
Pages
596-609
Publisher
American Society of Hematology
Description
Overcoming drug resistance and targeting cancer stem cells remain challenges for curative cancer treatment. To investigate the role of microRNAs (miRNAs) in regulating drug resistance and leukemic stem cell (LSC) fate, we performed global transcriptome profiling in treatment-naive chronic myeloid leukemia (CML) stem/progenitor cells and identified that miR-185 levels anticipate their response to ABL tyrosine kinase inhibitors (TKIs). miR-185 functions as a tumor suppressor: its restored expression impaired survival of drug-resistant cells, sensitized them to TKIs in vitro, and markedly eliminated long-term repopulating LSCs and infiltrating blast cells, conferring a survival advantage in preclinical xenotransplantation models. Integrative analysis with mRNA profiles uncovered PAK6 as a crucial target of miR-185, and pharmacological inhibition of PAK6 perturbed the RAS/MAPK pathway and mitochondrial …
Scholar articles
H Lin, K Rothe, M Chen, A Wu, A Babaian, R Yen… - Blood, The Journal of the American Society of …, 2020