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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782187623955038208 |
---|---|
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. |
format | Text |
id | pubmed-2950084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | European Molecular Biology Organization |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT burchardjulja microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT zhangchunsheng microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT liuangelam microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT poonronnietp microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT leenikkipy microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT wongkwongfai microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT shampakc microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT lambriany microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT fergusonmarkd microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT tokiwageorge microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT smithryan microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT leesonbrendan microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT beardrebecca microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT lambjohnr microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT limlee microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT maomao microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT daihongyue microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma AT lukjohnm microrna122asaregulatorofmitochondrialmetabolicgenenetworkinhepatocellularcarcinoma |