Rapid advances in genotyping and sequencing technology have dramatically accelerated the discovery of genes underlying human disease. Elucidating the function of such genes and understanding their role in pathogenesis, however, remains challenging. Here, we introduce a genomic strategy to functionally characterize such genes, and apply it to LRPPRC (leucine-rich PPR-motif containing), a poorly studied gene that is mutated in Leigh Syndrome, French Canadian type (LSFC).
Mitochondrial and nuclear genomic responses to loss of LRPPRC expression.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Specimen part, Treatment
View SamplesTreatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination
Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of several compounds on the MCF7 human adenocarcinoma mammary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitors PHA-848125 and PHA-690509 on the A2780 cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitor PHA-793887 on the A2780 human adenocarcinoma ovary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitor PHA-848125 (referred to as CDK-125) on the MCF7 human adenocarcinoma mammary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe effects of the CDK inhibitor Flavopiridol on the A2780 human adenocarcinoma ovary cell line were analysed by gene expression profiling.
Discovery of drug mode of action and drug repositioning from transcriptional responses.
Specimen part, Cell line, Treatment
View SamplesThe p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal-regulated kinase (ERK) signaling, can mediate cross-talk with the mammalian target of rapamycin complex 1 (mTORC1) pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1-4 in non-tumoral brain (NB) and grade I-IV gliomas. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBMs demonstrating the lowest RSK3 protein levels. When compared to NB or low-grade gliomas (LGG), a group of glioblastomas (RSK1hi) that excluded long-survivor cases expressed higher levels of RSK1. No difference was observed in RSK2 median-expression levels among NB and gliomas; however, high levels of RSK2 in glioblastomas (GBM) were associated with worse survival. RSK1hi and, to a lesser extent, RSK2hi GBMs, showed higher levels of phosphorylated RSK, which indicates RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated-natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long-survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker LAPTM5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform-specific peculiarities. The progression-dependent expression and association with immune infiltration, suggests RSK1 as a potential progression marker and therapeutic target for gliomas.
Aberrant expression of RSK1 characterizes high-grade gliomas with immune infiltration.
Specimen part
View Samples