Imperial College London
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DrJonathanKrell

Faculty of Medicine, Department of Surgery & Cancer

Clinical SL in Medical Oncology (Gynaecological Oncology)
 
 
 
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Contact

 

j.krell

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Castellano:2017:nar/gkx022,
author = {Castellano, L and Dabrowska, A and Pellegrino, L and Ottaviani, S and Cathcart, P and Frampton, A and Krell, J and Stebbing, J},
doi = {nar/gkx022},
journal = {Nucleic Acids Research},
pages = {4401--4412},
title = {Sustained expression of miR-26a promotes chromosomal instability and tumorigenesis through regulation of CHFR},
url = {http://dx.doi.org/10.1093/nar/gkx022},
volume = {45},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - MicroRNA 26a (miR-26a) reduces cell viability in several cancers, indicating that miR-26a could be used as a therapeutic option in patients. We demonstrate that miR-26a not only inhibits G1-S cell cycle transition and promotes apoptosis, as previously described, but also regulates multiple cell cycle checkpoints. We show that sustained miR-26a over-expression in both breast cancer (BC) cell lines and mouse embryonic fibroblasts (MEFs) induces oversized cells containing either a single-large nucleus or two nuclei, indicating defects in mitosis and cytokinesis. Additionally, we demonstrate that miR-26a induces aneuploidy and centrosome defects and enhances tumorigenesis. Mechanistically, it acts by targeting G1-S transition genes as well as genes involved in mitosis and cytokinesis such as CHFR, LARP1 and YWHAE. Importantly, we show that only the re-expression of CHFR in miR-26a over-expressing cells partially rescues normal mitosis and impairs the tumorigenesis exerted by miR-26a, indicating that CHFR represents an important miR-26a target in the regulation of such phenotypes. We propose that miR-26a delivery might not be a viable therapeutic strategy due to the potential deleterious oncogenic activity of this miRNA.
AU  - Castellano,L
AU  - Dabrowska,A
AU  - Pellegrino,L
AU  - Ottaviani,S
AU  - Cathcart,P
AU  - Frampton,A
AU  - Krell,J
AU  - Stebbing,J
DO  - nar/gkx022
EP  - 4412
PY  - 2017///
SN  - 1362-4962
SP  - 4401
TI  - Sustained expression of miR-26a promotes chromosomal instability and tumorigenesis through regulation of CHFR
T2  - Nucleic Acids Research
UR  - http://dx.doi.org/10.1093/nar/gkx022
UR  - http://hdl.handle.net/10044/1/43817
VL  - 45
ER  -
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