Effect of Runx2 Knockdown by siRNA in granulosa cell cultures.
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE20246 | GEO | 2010/02/10
SECONDARY ACCESSION(S): PRJNA124209
REPOSITORIES: GEO
Similar Datasets
Project description:LH-indced RUNX2 expression is important for luteal gene expression. Granulosa cells were treated with Runx2 siRNA and forskolin to knockdown agonist-induced Runx2 expression. Two separate cultures were performed (n=2) and universal siRNA was used for negative control. Total RNAs were isolated from cultured granulosa cells and used for DNA microarray.
2010-02-22 | E-GEOD-20246 | biostudies-arrayexpress
Project description:Human granulosa cells are follicular cells surrounding the oocyte. Human granulosa cells are retrieved during in vitro fertilization a process where patients undergo hormonal stimulation including FSH and LH/hCG stimulation. Under the influence of the luteinizing hormone (LH) a process called luteinization they differentiate to luteal cells and contribute to the corpus luteum. Therefore, this cellular system is a good model for human corpus luteum (CL). To study processes within the human CL, IVF-derived GCs from patients were cultured for two to five days and then analyzed with mass spectrometry based shotgun proteomics.
2019-03-07 | PXD010658 | Pride
Project description:Cells of MDA-MB-231 breast cancer cell-line were transfected with siRNA against Runx2, CBF-beta or non-specific siRNA used as control. Runx2 is a member of the Runx transcription factor family and possesses a Runt domain capable of binding to the consensus DNA sequence ACC(A/G)CA. This domain also interacts with the co-activator protein core binding factor beta (CBF-beta), which enhances its binding to DNA. Runx2, primarily identified as a master regulator of bone development, but was also found expressed in the epithelium of the nascent mammary gland in mice. In contrast with its normal role in breast, it has been shown that Runx2 is over-expressed in breast cancer cell lines.
2011-10-19 | E-MEXP-3230 | biostudies-arrayexpress
Project description:The LH surge is a pivotal event that triggers multiple key ovarian processes including oocyte maturation, cumulus expansion, follicular wall rupture and luteinization of mural granulosa and theca cells. Recently, LH-dependent activation of the Hippo signaling pathway has been shown to be required for the differentiation of granulosa cells into luteal cells. This study aimed to better characterize the role of the Hippo pathway in the LH response in murine granulosa cells. In order to highlight specific roles of Hippo in murine GC physiology, we conducted a microarray analysis to identify genes differentially expressed in cultured granulosa cells with knocked-down expression of YAP1/TAZ (the two co-regulators of Hippo signaling).
2022-01-01 | GSE184396 | GEO
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with a high incidence of relapse. Here we show that Runt-related transcription factor 2, RUNX2 is upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or immature phenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, while it reciprocally binds the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 is required for survival in immature and KMT2A-R T-ALL in vitro and in vivo. We report a direct transcriptional regulation of CXCR4 signaling by RUNX2, which thereby promotes cell migration and adhesion. Functionally, RUNX2 impacts T-ALL cell homing and exacerbates T-ALL progression to medullary and extramedullary sites. We demonstrate that RUNX2 enables these energy-demanding processes by increasing metabolic activity in T-ALL cells through positive regulation of both glycolysis and oxidative phosphorylation. Concurrently, RUNX2 upregulation results in increased mitochondrial dynamics and biogenesis in T-ALL cells. As a proof of concept, immature and KMT2A-R T-ALL cells are vulnerable to pharmacological targeting of the interaction of RUNX2 with its co-factor CBFβ. In conclusion, we identify RUNX2 a dependency factor in immature and KMT2A-R T-ALL that regulates cell metabolism and disease progression
2020-06-05 | GSE151820 | GEO
Project description:A large body of evidence suggests that the development and maintenance of corpus luteum (CL) in primates requires the action of LH. Earlier, using CET-induced luteolysis model, we demonstrated changes in luteal transcriptome suggesting nuclear actions of LH in the primate CL. To further demonstrate the role of LH in maintenance of primate CL, replacement studies were carried out and it was observed that administration of a single injection of rhLH was sufficient to restore the progesterone to pre-CET treatment levels and prevent the CET-induced luteolysis. To elucidate the molecular mechanisms underlying the rescue of CL function, we used LH-replacement model to study immediate early changes in gene expression at a global level (Affymetrix oligonucleotide microarray) following LH replacement in CET-treated monkeys and to evaluate if the changes in gene expression mediated by LH-withdrawal can be reversed by LH replacement. Results demonstrated up-and down-regulation of various genes following LH replacement and suggested that LH-withdrawal induced changes in gene expression are reversible at least for some genes. Keywords: CL, CET, rhLH
2007-07-06 | GSE8371 | GEO
Project description:Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/- and double mutant Axin2-/-:Runx2+/- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. 4 mice per genotype X 4 genotypes: wildtype (WT), Runx2+/- (R-Het), Axin2-/- (A-KO), Axin2-/-:Runx2+/- (A-KO:R-Het). Total = 16 samples
2014-07-04 | E-GEOD-59079 | biostudies-arrayexpress
Project description:Granulosa cells from three different stages were used to assess the short- and long-term effects of luteinizing hormone (LH) on follicle differentiation: 1) 2 h before induction of the LH surge, 2) 6 h and 3) 22 h after the LH surge. Three time points experiment: 2h pre-LH, 6h post-LH and 22h post-LH. Granulosa cells from the 6h post-LH and 22h post-LH were compared to the 2h pre-LH. Biological replicates: 4 from each time point. One replicate per array. Dye-swaps were performed.
2015-05-27 | E-GEOD-69247 | biostudies-arrayexpress
Project description:Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/-M-BM- mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/-M-BM- mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2-/-:Runx2+/-mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/-M-BM- mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2-/-:Runx2+/-calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/-M-BM- and double mutant Axin2-/-:Runx2+/-M-BM- mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/-M-BM- mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2-/-M-BM- mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. 4 mice per genotype X 4 genotypes: wildtype (WT), Runx2+/- (R-Het), Axin2-/- (A-KO), Axin2-/-:Runx2+/- (A-KO:R-Het). Total = 16 samples
2014-07-04 | E-GEOD-59081 | biostudies-arrayexpress
Project description:Transcription factors, by acting on gene expression can affect molecular pathways and can thereby induce malignant transformation. Among the transcription factors involved in cellular transformation, we recently highlighted the role of RUNX2 in melanoma cell migration and proliferation. In the present study, we extended the analysis of the molecular effects of RUNT domain of RUNX2 in melanoma cells to deepen understanding of the underlying mechanisms. By the CRISPR/Cas9 system we generated the RUNT KO melanoma cells 3G8. Therefore, using a proteomic approach, we compared 3G8 with the original wild-type melanoma cell line (A375). The results showed a specific protein signature of 3G8 cells related to apoptosis and migration. In addition, proteomic analysis allowed us to point out the involvement of the RUNT domain in the neoangiogenesis process. Among the deregulated proteins implicated in angiogenesis we found fatty acid synthase, chloride intracellular channel protein-4, heat shock protein beta-1, Rho guanine nucleotide exchange factor 1, D-3-phosphoglycerate dehydrogenase, myosin-1c and caveolin-1. Accordingly, the VEGF gene expression was higher in A375 compared to 3G8 cells; HUVEC cells expressed increased levels of the neoangiogenetic markers CD105 and CD31 when co-cultured with A375 cells. In conclusion, our study provided new insight into RUNX2 molecular details which can be crucial to possibly propose it as an oncotarget of melanoma.
2019-11-13 | PXD012096 | Pride