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MiRNA expression profiles of PRC SiRNA vs scramble transfected XTC.UC1 cells

ABSTRACT: PGC-1 related coactivator (PRC) shares structural and functional features with PGC-1{alpha}. It regulates several metabolic pathways and mitochondrial biogenesis. Its specific role in the early programming of cell proliferation suggests a finely regulated crosstalk between the mitochondrial functions and the cell cycle status. To explore the PRC-regulated pathways, we used a cell-line model of mitochondrial-rich tumors, presenting an oxidative metabolism and a specific increase in PRC expression. We looked for the feedback loop exerted by miRNAs on the regulation of PRC-related mitochondiral functions Expression profiles of miRNA at 48h PRC SIRNA treatment compared to scramble in XTC.UC1 cells. In duplicate.

ORGANISM(S): Homo sapiens

SUBMITTER: frederique savagner

PROVIDER: E-GEOD-33843 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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PRC SiRNA vs scramble transfection in XTC.UC1 cells

Project description:PGC-1 related coactivator (PRC) shares structural and functional features with PGC-1{alpha}. It regulates several metabolic pathways and mitochondrial biogenesis. Its specific role in the early programming of cell proliferation suggests a finely regulated crosstalk between the mitochondrial functions and the cell cycle status. To explore the PRC-regulated pathways, we used a cell-line model of mitochondrial-rich tumors, presenting an oxidative metabolism and a specific increase in PRC expression. Microarray studies of temporal PRC invalidation in these XTC.UC1 cells were compared to the functional status of the mitochondria as well as to the expression level of genes and proteins involved in the oxidative phosphorylation process. Compared with what was observed for PGC-1{alpha}, we explored the role of nitric oxide in the PRC-regulated mitochondrial biogenesis. We proved that nitric oxide rapidly influences the expression of PRC at the transcriptional level. Focusing on mitochondrial energy metabolism, we demonstrated that PRC differentially controls the respiratory chain complexes and the coupling efficiency, in order to conserve a sufficient level of ATP and to protect the cell from oxidative stress. Our results highlight the key role of the PRC coactivator in the fine modulation of metabolic functions in response to the cell cycle status. Keywords: Transcriptionnal coactivator invalidation by SiRNA Expression profiles at 0h, 12h, 24h and 48h of PRC SIRNA treatment compared to scramble and referred to time of 20% serum induction. Expression profiles of PRC SIRNA and scramble during serum starvation were referred as -1.

2010-05-14 | E-GEOD-14282 | biostudies-arrayexpress

PRC SiRNA vs scramble transfection in XTC.UC1 cells

2009-01-07 | GSE14282 | GEO

miRNA expression profiles of PRC SiRNA vs scramble transfected XTC.UC1 cells

2011-11-22 | GSE33843 | GEO

Effects of plasmids transfection on the RO82_W1 human thyroid cell line

Project description:The goal of this study was to identifiy cellular pathways modified by RO82_W1 cell transfection with PRC, ERRalpha or PRC+ERRalpha plamids relative to transfection with PGl3 plasmid In duplicate, cells transfected with PRC, ERRalpha or PRC+ERRalpha plamids during 48h compared to PGl3 treated cells

2012-05-31 | E-GEOD-37240 | biostudies-arrayexpress

Transcription profiling of Drosophila Spargel mutant versus genetically matched wildtype control

Project description:Mammalian PGC-1alpha, PGC-1beta and PRC are structurally related transcriptional coactivators, and are involved in multiple metabolic functions, including the regulation of mitochondrial biogenesis. However, due to redundancy, their in vivo roles are still poorly understood. By a genome-wide microarray study, we show that in the Drosophila larval fat body, Spargel (CG9809), the only fly PGC-1 family homologue, is required for proper expression of multiple genes encoding mitochondrial proteins. Experiment Overall Design: Six samples were analyzed in total: three biological replicates of the control (wt) and three biological replicates of the mutant (KG).

2009-02-21 | E-GEOD-14780 | biostudies-arrayexpress

Gene expression analysis of spargel mutant versus genetically matched wildtype control

2009-02-13 | GSE14780 | GEO

Physiological defects associated with short hairpin RNA-mediated silencing of PGC-1-related coactivator (PRC)

Project description:PRC, a member of the PGC-1 coactivator family, is responsive to serum growth factors and up regulated in proliferating cells. Here, we investigated its in vivo role by stably silencing PRC expression with two different short hairpin RNAs (shRNA#1 and shRNA#4) that were lentivirally introduced into U2OS cells. ShRNA#1 transductants exhibited nearly complete knockdown of PRC protein whereas shRNA#4 transductants expressed PRC protein at approximately 15 percent of the control level. Complete PRC silencing by shRNA#1 resulted in a severe inhibition of respiratory growth, reduced expression of respiratory protein subunits from complexes I, II, III and IV, markedly lower complex I and IV respiratory enzyme levels and diminished mitochondrial ATP production. Surprisingly, shRNA#1 transductants exhibited a striking proliferation of abnormal mitochondria that were devoid of organized cristae and displayed severe membrane abnormalities. Although shRNA#4 transductants had normal respiratory subunit expression and a moderately diminished respiratory growth rate, both transductants showed markedly reduced growth on glucose accompanied by inhibition of G1/S cell cycle progression. Microarray analysis revealed striking overlaps in the genes affected by PRC silencing in the two transductants and the functional identities of these overlapping genes were consistent with the observed mitochondrial and cell growth phenotypes. The consistency between phenotype and PRC expression levels in the two independent transductant lines argues that the defects result from PRC silencing and not from off target effects. These results support a role for PRC in the integration of pathways directing mitochondrial respiratory function and cell growth.

2009-01-16 | GSE14428 | GEO

Mastermind-like protein 1 regulates DNA methylation and expression of early developmental gene clusters in human embryonic kidney cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-10-08 | E-GEOD-62178 | biostudies-arrayexpress

Transcription profiling of differentiated brown adipocytes from wild type, PGC-1 alpha knockout, or PGC-1 alpha knockout and PGC-1 beta knockdown mice to investigate the roles of PGC-1 coactivators in brown fat differentiation.

Project description:Mitochondria play an essential role in the ability of brown fat to generate heat, and the PGC-1 coactivators control several aspects of mitochondrial biogenesis. To investigate their specific roles in brown fat cells, we generated immortal preadipocyte lines from the brown adipose tissue of mice lacking PGC-1±. We could then efficiently knockdown PGC-1Î² expression by shRNA expression. Loss of PGC-1± did not alter brown fat differentiation but severely reduced the induction of thermogenic genes. Cells deficient in either PGC-1Î± or PGC-1Î² coactivators showed a small decrease in the differentiation-dependant program of mitochondrial biogenesis and respiration; however, this increase in mitochondrial number and function was totally abolished during brown fat differentiation when both PGC-1± and PGC-1 were deficient. These data show that PGC-1± is essential for brown fat thermogenesis but not brown fat differentiation, and the PGC-1 coactivators play an absolutely essential but complementary function in differentiation-induced mitochondrial biogenesis. Affymetrix microarray analysis of total RNA from wt, PGC-1± KO and PGC-1± KO; cells expressing an RNAi specific for PGC-1 knockdown was performed. Of the 461; mitochondrial genes analyzed, 181 were found to be at least 20% different between wt; and defective PGC-1± and Î² adipocytes (p < 0.05). More than 85% of these genes were downregulated in cells deficient for PGC-1alpha and PGC-1beta. Experiment Overall Design: Brown preadipocytes that were either WT, KO for PGC-1alpha, or KO for PGC-1alpha and deficient for PGC-1beta (knockdown through siRNA expression) were differentiated for seven days. RNA was made from biological replicates of the three different types of brown adipocytes (WT, KO expressing a control siRNA, KO expressing a siRNA specific for PGC-1beta knockdown).

2007-11-27 | E-GEOD-5042 | biostudies-arrayexpress

Microarray of cardiac biventricle from PGC-1a-/-bf/f/MerCre mice

Project description:The following abstract from the submitted manuscript describes the major findings of this work. The metabolic development of high energy-utilizing organs such as the heart involves mitochondrial proliferation at birth followed by a maturation process during the postnatal period. Conditional gene targeting was used in mice to explore the role of the PPARgamma coactivator 1 (PGC-1) coactivators during postnatal development and in adult heart. Marked mitochondrial derangements were observed in hearts of PGC-1a/b-deficient mice during the postnatal period, including fragmentation and elongation associated with the development of a lethal cardiomyopathy. The expression of multiple genes involved in mitochondrial fusion and fission was downregulated in hearts of PGC-1a/b-deficient mice. PGC-la was shown to activate transcription of the mitofusin 1 (Mfn1) gene by coactivating the estrogen-related receptor a (ERRa) upon a highly conserved element. Surprisingly, PGC-1a/b deficiency did not alter cardiac function or general mitochondrial density and myocyte distribution in adult heart. However, transcriptional profiling and mitochondrial function studies demonstrated that the PGC-1 coactivators are required for full respiratory capacity and high level expression of nuclear- and mitochondrial-encoded genes involved in mitochondrial energy transduction and oxidative phosphorylation pathways in adult heart. These results unveil distinct developmental stage-specific transcriptional programs involved in the maturation and maintenance of mitochondria. RNA from five PGC-1a-/- and five PGC-1a-/-bf/f/MerCre mice was analyzed.

2014-01-13 | E-GEOD-43798 | biostudies-arrayexpress

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