Journal
CANCER LETTERS
Volume 388, Issue -, Pages 107-117Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.11.035
Keywords
Pancreatic cancer; microRNA; Multi drug resistance; Novel therapeutics
Categories
Funding
- Society of Friends of the University of Heidelberg e.V. (GdF)
- Federal Ministry of Education and Research [BMBF 031A213]
- Heidelberger Surgery Foundation
- Foundation for Cancer- and Scarlet-Research
- Dietmar Hopp-Foundation
- Hanns A. Pielenz-Foundation
- Deutsche Forschungsgemeinschaft
- Ruprecht-Karls-Universitat Heidelberg
Ask authors/readers for more resources
Resistance to first-line chemotherapies like gemcitabine contributes to high disease lethality in pancreatic cancer. By microarray and qRT-PCR, we observed significant downregulation of microRNA-210 in gemcitabine-resistant cells. The overexpression of microRNA-210 was toxic to gemcitabine resistant cells and enhanced gemcitabine sensitivity. MicroRNA-210 overexpression induced caspase-3-mediated apoptosis, and inhibited colony formation. Computationally, ABCC5, a highly expressed gene in our array data, was identified as a potential target of microRNA-210 and the over expression of ABCC5 in gemcitabine-resistant cells was confirmed by qRT-PCR. MicroRNA-210 over expression reduced ABCC5 mRNA levels and inhibited a luciferase reporter expressing the ABCC5 3' UTR. The expression pattern of microRNA-210 and ABCC5 was mirrored in all of 5 pancreatic cancer cell lines used. Likewise, microRNA-210 transfection nearly totally inhibited tumor xenograft growth, proliferation and metastasis without obvious side effects in vivo. Also, an absence or low expression of microRNA-210 correlated to high ABCC5 expression in the majority of malignant patient tissues from a total of 101 patient tissues examined. Our observations provide at first glance, an important function for microRNA-210 in regulation of gemcitabine responsiveness by it's target gene ABCC5. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available