Imperial College London
Portrait Picture

DrChunghoLau

Faculty of Medicine, School of Public Health

Research Associate
 
 
 
//

Contact

 

chungho.lau Website

 
 
//

Location

 

Sir Michael Uren HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Keun:2015:10.1038/onc.2015.333,
author = {Keun, H and Koufaris, C and Ellis, J and Yang, T and benito, mauricio A and tredwell, G and lau, C and nevedomskya, E and pomyen, Y and valbuena, G},
doi = {10.1038/onc.2015.333},
journal = {Oncogene},
pages = {2766--2776},
title = {Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells},
url = {http://dx.doi.org/10.1038/onc.2015.333},
volume = {35},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Dysregulated microRNA (miRNA) mediate malignant phenotypes, including metabolic reprogramming. By performing an integrative analysis of miRNA and metabolome data for the NCI-60 cell line panel, we identified an miRNA cluster strongly associated with both c-Myc expression and global metabolic variation. Within this cluster the cancer-associated and cardioprotective miR-22 was shown to repress fatty acid synthesis and elongation in tumour cells by targeting ATP citrate lyase and fatty acid elongase 6, as well as impairing mitochondrial one-carbon metabolism by suppression of methylene tetrahydrofolate dehydrogenase/cyclohydrolase. Across several data sets, expression of these target genes were associated with poorer outcomes in breast cancer patients. Importantly, a beneficial effect of miR-22 on clinical outcomes in breast cancer was shown to depend on the expression levels of the identified target genes, demonstrating the relevance of miRNA/mRNA interactions to disease progression in vivo. Our systematic analysis establishes miR-22 as a novel regulator of tumour cell metabolism, a function that could contribute to the role of this miRNA in cellular differentiation and cancer development. Moreover, we provide a paradigmatic example of effect modification in outcome analysis as a consequence of miRNA-directed gene targeting, a phenomenon that could be exploited to improve patient prognosis and treatment.
AU  - Keun,H
AU  - Koufaris,C
AU  - Ellis,J
AU  - Yang,T
AU  - benito,mauricio A
AU  - tredwell,G
AU  - lau,C
AU  - nevedomskya,E
AU  - pomyen,Y
AU  - valbuena,G
DO  - 10.1038/onc.2015.333
EP  - 2776
PY  - 2015///
SN  - 1476-5594
SP  - 2766
TI  - Systematic integration of molecular profiles identifies miR-22 as a regulator of lipid and folate metabolism in breast cancer cells
T2  - Oncogene
UR  - http://dx.doi.org/10.1038/onc.2015.333
UR  - http://hdl.handle.net/10044/1/29953
VL  - 35
ER  -
Download