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Series GSE22058 Query DataSets for GSE22058
Status Public on Jun 09, 2010
Title miR-122 as a Regulator of Mitochondrial Metabolic Gene Network in Hepatocellular Carcinoma
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Other
Summary Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide, reflecting the need for a better understanding of hepatocarcinogenesis. In this study, we examined the genome-wide expression profiles of both miRNAs and mRNAs from paired tumor and adjacent non-tumor tissues from a cohort of 96 HCC patients in Hong Kong where hepatitis B virus (HBV) is endemic. The comprehensive analysis of the coordinate expression of miRNAs and mRNAs reveals that miR-122 is under-expressed in HCC and that it is an important regulator for normal mitochondrial metabolism. A decreased level of miR-122 leads to an increase in expression of miR-122 seed-matched genes, a loss of mitochondrial metabolic function, and a decrease in the expression of many miR-122 secondary targets. These secondary targets are prognostic markers for HCC patients. Transcriptome profiling data from an 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. To test the HCC findings in normal mouse liver, we used an antagomir against miR-122 and identified altered gene expression profiling by microarray analysis in mouse in vivo experiments. The mouse data recapitulated the human HCC findings. Our anti-miR122 data further provided a direct link between increases in the mRNA levels of miR-122 controlled genes and impairments of mitochondrial metabolism. In summary, we find miR-122 loss may be detrimental to mitochondrial-related metabolisms in sustaining critical liver function and contribute to the morbidity and mortality of liver cancer patients.
 
Overall design Mouse liver profiling:
In one treatment regimen, four animals were given four doses of 100mg ASO/kg body weight, administered every other day, and sacrificed one day after the last dose. Four animals treated for four weeks were treated twice weekly with 50mg ASO/kg body weight, and sacrificed two days after the last dose. Mice were sacrificed in the morning, and liver was removed for further analysis. Samples from oligonucleotide-treated mice were referenced against samples from saline-treated mice in fluor-reversed pairs.

Human liver profiling:
For human HCC patient samples, 192 samples -- 96 resected tumor and 96 adjacent non-tumor liver tissues -- were collected from 96 patients who had undergone hepatectomy for curative treatment of HCC at Queen Mary Hospital, Pokfulam, Hong Kong between 1990 and 2007. Informed consents were obtained from patients regarding the use of the liver specimens for research. Samples were hybridized to Affymetrix arrays for mRNA profiling and were analyzed by quantitative PCR for microRNA profiling.
 
Contributor(s) Burchard J, Zhang C, Liu AM, Lee NP, Wong K, Poon RT, Sham PC, Lam BY, Ferguson MD, Tokiwa G, Smith R, Leeson B, Beard R, Lamb JR, Lim L, Mao M, Dai H, Luk JM
Citation(s) 20739924, 22403344
Submission date May 30, 2010
Last update date Jan 18, 2013
Contact name Julja Burchard
Organization name Merck & Co., Inc.
Department Computational & Systems Biology
Street address 33 Avenue Louis Pasteur
City Boston
State/province MA
ZIP/Postal code 02176
Country USA
 
Platforms (3)
GPL6793 Rosetta/Merck Human RSTA Custom Affymetrix 1.0 microarray
GPL9733 Rosetta/Merck Mouse 23.6K 3.0 A1 microarray
GPL10457 Rosetta human miRNA qPCR array
Samples (397)
GSM548033 Saline 1 vs. miR-122 antagomir, mouse 1, mouse liver, 1 month
GSM548034 Saline 2 vs. miR-122 antagomir, mouse 2, mouse liver, 1 month
GSM548035 Saline 3 vs. miR-122 antagomir, mouse 3, mouse liver, 1 month
Relations
BioProject PRJNA128963

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE22058_RAW.tar 704.8 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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