Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profile of HCCs developed in miR-122 knockout mice compared to age-matched wild type mice

ABSTRACT: Gene expression profiling of HCCs developed in miR-122 knockout mice compared to age-matched wild type mice. The significance of our study is that miR-122 knockout mice spontaneously develop liver tumors and the gene expression profile demonstrated dysregulation of several pathways involved in liver disease and HCC. Two-condition experiment, liver tumor vs. normal liver. 8 biological replicates.

ORGANISM(S): Mus musculus

SUBMITTER: kalpana ghoshal

PROVIDER: E-GEOD-31731 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver.

Hsu Shu-Hao SH Wang Bo B Kota Janaiah J Yu Jianhua J Costinean Stefan S Kutay Huban H Yu Lianbo L Bai Shoumei S La Perle Krista K Chivukula Raghu R RR Mao Hsiaoyin H Wei Min M Clark K Reed KR Mendell Jerry R JR Caligiuri Michael A MA Jacob Samson T ST Mendell Joshua T JT Ghoshal Kalpana K

The Journal of clinical investigation 20120723 8

miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathol ...[more]

PMID: 22820288

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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

Gene expression profile of HCCs developed in miR-122 knockout mice compared to age-matched wild type mice

Publications

Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver.

Similar Datasets

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