microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma

Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)–gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate e...

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Autores principales: Burchard, Julja, Zhang, Chunsheng, Liu, Angela M, Poon, Ronnie T P, Lee, Nikki P Y, Wong, Kwong-Fai, Sham, Pak C, Lam, Brian Y, Ferguson, Mark D, Tokiwa, George, Smith, Ryan, Leeson, Brendan, Beard, Rebecca, Lamb, John R, Lim, Lee, Mao, Mao, Dai, Hongyue, Luk, John M
Formato: Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950084/
https://www.ncbi.nlm.nih.gov/pubmed/20739924
http://dx.doi.org/10.1038/msb.2010.58
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author Burchard, Julja
Zhang, Chunsheng
Liu, Angela M
Poon, Ronnie T P
Lee, Nikki P Y
Wong, Kwong-Fai
Sham, Pak C
Lam, Brian Y
Ferguson, Mark D
Tokiwa, George
Smith, Ryan
Leeson, Brendan
Beard, Rebecca
Lamb, John R
Lim, Lee
Mao, Mao
Dai, Hongyue
Luk, John M
author_facet Burchard, Julja
Zhang, Chunsheng
Liu, Angela M
Poon, Ronnie T P
Lee, Nikki P Y
Wong, Kwong-Fai
Sham, Pak C
Lam, Brian Y
Ferguson, Mark D
Tokiwa, George
Smith, Ryan
Leeson, Brendan
Beard, Rebecca
Lamb, John R
Lim, Lee
Mao, Mao
Dai, Hongyue
Luk, John M
author_sort Burchard, Julja
collection PubMed
description Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)–gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122-controlled genes and impairment of mitochondrial metabolism. In conclusion, miR-122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients.
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spelling pubmed-29500842010-10-05 microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma Burchard, Julja Zhang, Chunsheng Liu, Angela M Poon, Ronnie T P Lee, Nikki P Y Wong, Kwong-Fai Sham, Pak C Lam, Brian Y Ferguson, Mark D Tokiwa, George Smith, Ryan Leeson, Brendan Beard, Rebecca Lamb, John R Lim, Lee Mao, Mao Dai, Hongyue Luk, John M Mol Syst Biol Article Tumorigenesis involves multistep genetic alterations. To elucidate the microRNA (miRNA)–gene interaction network in carcinogenesis, we examined their genome-wide expression profiles in 96 pairs of tumor/non-tumor tissues from hepatocellular carcinoma (HCC). Comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that increased expression of miR-122 seed-matched genes leads to a loss of mitochondrial metabolic function. Furthermore, the miR-122 secondary targets, which decrease in expression, are good prognostic markers for HCC. Transcriptome profiling data from additional 180 HCC and 40 liver cirrhotic patients in the same cohort were used to confirm the anti-correlation of miR-122 primary and secondary target gene sets. The HCC findings can be recapitulated in mouse liver by silencing miR-122 with antagomir treatment followed by gene-expression microarray analysis. In vitro miR-122 data further provided a direct link between induction of miR-122-controlled genes and impairment of mitochondrial metabolism. In conclusion, miR-122 regulates mitochondrial metabolism and its loss may be detrimental to sustaining critical liver function and contribute to morbidity and mortality of liver cancer patients. European Molecular Biology Organization 2010-08-24 /pmc/articles/PMC2950084/ /pubmed/20739924 http://dx.doi.org/10.1038/msb.2010.58 Text en Copyright © 2010, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-nd/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial No Derivative Works 3.0 Unported License, which permits distribution and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation or the creation of derivative works without specific permission.
spellingShingle Article
Burchard, Julja
Zhang, Chunsheng
Liu, Angela M
Poon, Ronnie T P
Lee, Nikki P Y
Wong, Kwong-Fai
Sham, Pak C
Lam, Brian Y
Ferguson, Mark D
Tokiwa, George
Smith, Ryan
Leeson, Brendan
Beard, Rebecca
Lamb, John R
Lim, Lee
Mao, Mao
Dai, Hongyue
Luk, John M
microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
title microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
title_full microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
title_fullStr microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
title_full_unstemmed microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
title_short microRNA-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
title_sort microrna-122 as a regulator of mitochondrial metabolic gene network in hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950084/
https://www.ncbi.nlm.nih.gov/pubmed/20739924
http://dx.doi.org/10.1038/msb.2010.58
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