Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide analysis of gene expression patterns in the liver tumors of mir-122 knockout mice

ABSTRACT: To invesigate the physiological roles of mir-122 in hepatocarcinogenesis, we performed expression profiling of the liver tumors of mir-122 knockout mice and the liver tissues of the control B6/129 mice. Total RNA was extracted from three tumors of mir-122 knockout mice and liver tissues of two control mice of 11 months of age; five tumors of mir-122 knockout mice and the liver tissues of three control mice of 14 months of age. Gene expression was quantified by robust multi-array analysis (RMA) using the Genomic Suite software from Partek.

ORGANISM(S): Mus musculus

SUBMITTER: Ann-Ping Tsou

PROVIDER: E-GEOD-31453 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis.

Tsai Wei-Chih WC Hsu Sheng-Da SD Hsu Chu-Sui CS Lai Tsung-Ching TC Chen Shu-Jen SJ Shen Roger R Huang Yi Y Chen Hua-Chien HC Lee Chien-Hsin CH Tsai Ting-Fen TF Hsu Ming-Ta MT Wu Jaw-Ching JC Huang Hsien-Da HD Shiao Ming-Shi MS Hsiao Michael M Tsou Ann-Ping AP

The Journal of clinical investigation 20120723 8

MicroRNA-122 (miR-122), which accounts for 70% of the liver's total miRNAs, plays a pivotal role in the liver. However, its intrinsic physiological roles remain largely undetermined. We demonstrated that mice lacking the gene encoding miR-122a (Mir122a) are viable but develop temporally controlled steatohepatitis, fibrosis, and hepatocellular carcinoma (HCC). These mice exhibited a striking disparity in HCC incidence based on sex, with a male-to-female ratio of 3.9:1, which recapitulates the dis ...[more]

PMID: 22820290

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Project description:A defining feature of the mammalian liver is polyploidy, a numerical change in the entire complement of chromosomes. The first step of polyploidization involves cell division with failed cytokinesis. Although polyploidy is common, affecting ~90% of hepatocytes in mice and 50% in humans, the specialized role played by polyploid cells in liver homeostasis and disease remains poorly understood. The goal of this study was to identify novel signals that regulate polyploidization, and we focused on microRNAs (miRNAs). First, to test whether miRNAs could regulate hepatic polyploidy we examined livers from Dicer1 liver-specific knockout mice, which are devoid of mature miRNAs. Loss of miRNAs resulted in a 3-fold reduction in binucleate hepatocytes, indicating that miRNAs regulate polyploidization. Secondly, we surveyed age-dependent expression of miRNAs in wild-type mice and identified a subset of miRNAs, including miR-122, that is differentially expressed at 2-3 weeks, a period when extensive polyploidization occurs. Next, we examined Mir122 knockout mice and observed profound, life-long depletion of polyploid hepatocytes, proving that miR-122 is required for complete hepatic polyploidization. Moreover, the polyploidy defect in Mir122 knockout mice was ameliorated by adenovirus-mediated over-expression of miR-122, underscoring the critical role miR-122 plays in polyploidization. Finally, we identified direct targets of miR-122 (Cux1, Rhoa, Iqgap1, Mapre1, Nedd4l and Slc25a34) that regulate cytokinesis. Inhibition of each target induced cytokinesis failure and promoted hepatic binucleation. Conclusion: Our data demonstrate that miR-122 is both necessary and sufficient in liver polyploidization. Among the different signals that have been associated with hepatic polyploidy, miR-122 is the first liver-specific signal identified. These studies will serve as the foundation for future work investigating miR-122 in liver maturation, homeostasis and disease. Livers from C57Bl/6 mice were isolated at defined ages: embryonic day 15.5 (n=3; mixed gender), 2 weeks (n=3; male), 3 weeks (n=3, male) and 7 weeks (n=3; male). Differential miRNA expression was assessed using the nCounter Mouse miRNA Expression Assay Kit (nanoString).

Dataset Information

Genome-wide analysis of gene expression patterns in the liver tumors of mir-122 knockout mice

Publications

MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis.

Similar Datasets

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