The mitogen-activated protein kinase (MAPK) p38alpha controls inflammatory responses and cell proliferation. Using mice carrying conditional p38alpha alleles, we investigated its function in postnatal development and tumorigenesis. When p38alpha is specifically deleted in the mouse embryo, fetuses develop to term but die shortly after birth, likely due to lung dysfunction. Fetal hematopoietic cells and embryonic fibroblasts deficient in p38alpha display increased proliferation, resulting from sustained activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Importantly, in chemical-induced liver cancer development, mice with liver-specific deletion of p38alpha show enhanced hepatocyte proliferation and tumor development that also correlates with JNK/c-Jun upregulation. Furthermore, increased proliferation of p38alpha-deficient hepatocytes and tumor cells is suppressed by inactivation of JNK or c-Jun. These results reveal a novel mechanism whereby p38alpha negatively regulates cell proliferation through antagonizing the JNK/c-Jun pathway in multiple cell types and in liver cancer development.
p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway.
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View SamplesThousands of long intergenic noncoding RNAs (lincRNAs) are encoded by the mammalian genome, which were reported to have multiple biological functions as transcriptional activators acting in cis 1 or trans 2, transcriptional repressors 3,4 or miRNAs decoys 5,6. However, the function of most lincRNAs has not yet been identified in vivo. Here, we demonstrate a role for linc-MYH, a novel long intergenic noncoding RNA, in adult fast-type myofibre specialization. Skeletal myofibre fast and slow phenotypes are established through differential expression of numerous fibre-specific genes7. We show linc-MYH and the fast MYH genes share a common enhancer located in the fast MYH genes locus and regulated by the Six1 homeoproteins. Muscle-specific Six1 mutant mice show increased expression of slow-type genes, and downregulation of linc-MYH and fast-type genes. linc-MYH function revealed by in vivo knockdown and wide transcriptomic analysis, is in fine to prevent expression of genes ensuring slow muscle contractile properties, and to increase fast-type muscle gene expression in fast-type myofibres. Thus, formation of efficient fast sarcomeric units and appropriate Ca++ cycling and excitation/contraction/relaxation coupling in fast- myofibres is achieved through the coordiante control of fast MYHs and linc-MYH expression by a Six bound enhancer.
Six homeoproteins and a Iinc-RNA at the fast MYH locus lock fast myofiber terminal phenotype.
Age, Specimen part
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In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.
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View SamplesAPC is a key regulator of canonical Wnt signalling since it participates to beta-catenin targeting to proteasomal degradation when the pathway is inactive. Moreover, independently of Wnt signaling, APC regulates several cellular functions such as mycrotubule dynamics, chromosome segregation, cell adhesion. Although APC has been widely studied for its implication in initation and progression of several cancers, its role in satellite cells (skeletal muscle stem cells) has never been investigated.
APC is required for muscle stem cell proliferation and skeletal muscle tissue repair.
Specimen part
View SamplesGain or loss of genes and deregulation of gene expression can result in cumulative and progressive disruptions of normal cellular functions.
In vitro analysis of integrated global high-resolution DNA methylation profiling with genomic imbalance and gene expression in osteosarcoma.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesTranscriptome analysis of 130 breast cancer samples (41 TNBC; 30 Her2; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesTranscriptome analysis of 130 breast cancer samples (41 TNBC; 30 Her2; 30 Luminal B and 29 Luminal A), 11 normal breast tissue samples and 14 TNBC cell lines.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesWe analyzed the transcriptome of two different triple negative breast cancer (TNBC) cell lines to define a comprehensive list of Wnt target genes. Cells were treated with Wnt3a for 6h, 12h or 24h. We found up-regulated and down-regulated genes in response to Wnt3a treatment. They are involved in the Wnt pathway itself, and also in TGF, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific.
Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.
Cell line
View SamplesWe assessed the gene expression profile of purified CD205+CD8+ Dendritic Cells isolated from murine spleens.
NOD2 modulates immune tolerance via the GM-CSF-dependent generation of CD103<sup>+</sup> dendritic cells.
Sex, Age, Specimen part
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