Effect of Nr2f6 knockdown in C2C12 myocytes
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE229102 | GEO | 2024/04/05
REPOSITORIES: GEO
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Project description:Effect of Nr2f6 knockdown in C2C12 myocytes
| PRJNA952908 | ENA
Project description:Analysis of differentiating LSD1-KD C2C12 myoblasts. We found LSD1 is an important regulator of oxidative phenotypes in skeletal muscle cells. Results provide insight into the molecular mechanisms underlying roles of LSD1 in myocytes.
2018-03-19 | GSE109839 | GEO
Project description:Nuclear receptors (NRs) are implicated in the regulation of tumors and immune cells. We identify a tumor-intrinsic function of the orphan NR, NR2F6, regulating anti-tumor immunity. NR2F6 was selected from 48 candidate NRs, based on an expression pattern in melanoma patient specimens (i.e., IFN signature) associated with positive responses to immunotherapy and favorable patient outcomes. Correspondingly, genetic ablation of NR2F6 in a mouse melanoma model conferred a more effective response to PD-1 therapy. NR2F6 loss in B16F10 and YUMM1.7 melanoma cells attenuated tumor development in immune-competent but not -incompetent mice via the increased abundance of effector and progenitor-exhausted CD8+ T cells. Inhibition of NACC1 and FKBP10, identified as NR2F6 effectors, phenocopied NR2F6 loss. Remarkably, inoculation of NR2F6 KO mice with NR2F6 KD melanoma cells further decreased tumor growth compared with NR2F6 WT mice. Tumor-intrinsic NR2F6 function complements its tumor-extrinsic role and justifies the development of novel anti-cancer therapies.
2023-09-11 | GSE228162 | GEO
Project description:Orphan-Nuclear-Receptors (ONRs) are a group of ligand dependent transcriptional factors belonging to the family of Steroid-Nuclear-Receptors, which includes estrogen, progesterone and retinoic acid receptors. The ONR denomination refers to the fact that the endogenous ligands of these 15 nuclear receptors have not yet been identified. The vast majority of ONRs are expressed not only in normal tissues but also in different types of solid tumors, including various types of breast cancer. In the present study, we define the expression levels of the ONR mRNAs in a large panel of 51 cell-lines, which recapitulate the heterogeneity of breast cancer. Ten ONRs are characterized by a relatively high expression level in the majority of the breast cancer cell-lines considered and this is consistent with the high levels of the transcripts observed in mammary tumor tissues. To get insights into the functional role played by the 10 ONRs in the growth/progression of breast cancer, we silenced each receptor with a siRNA approach. Effective silencing of the NR2F2 receptor in 5 different and representative breast cancer cell-lines with two separate siRNAs results in an increased growth of each cell-line consistent with a tumor-suppressive action of the receptor. The effect is independent of the cell phenotype, as it is observed in Estrogen-Receptor and HER2 positive as well as Triple-Negative cell-lines. By converse, silencing of the NR2F6 receptor reduces the growth of the 5 selected cell-lines characterized by high expression levels of the ONR, suggesting an oncogenic action. Once again, the anti-proliferative effects of NR2F6 silencing are evident in all the cell-lines considered and are not associated with any of the 3 breast cancer phenotypes. Stable silencing of NR2F6 following infection of the Estrogen-Receptor positive MCF-7 and the Triple-Negative MDA-MB231 cell-lines with 2 specific and different shRNAs support the oncogenic properties of the ORF. Indeed, these shRNAs reduce the growth and clonogenic ability of the 2 cell-lines. In a first set of studies, we performed whole-genome RNA-sequencing experiments in the shRNA infected MCF-7 cells to get insights into the molecular mechanisms underlying the oncogenic action of NR2F6. Stable silencing of the NR2F6 mRNA and protein results in an up-regulation of the gene-networks involved in the pathways controlling cell-adhesion and cell-cell interactions. As expected, silencing causes down-regulation of the gene-networks involved in cell-cycle and cell-proliferation. In particular, we identify 50 and 9 genes whose expression is up-regulated and down-regulated by the knock-down of the NR2F6 transcription factor. These genes are likely to be direct or indirect targets of NR2F6 transcriptional activity. In a second set of experiments, we identify the endogenous organic molecules capable of interacting with the NR2F6 receptor using a mass-spectrometry based approach. To this purpose, we used NR2F6 immune-precipitates obtained from MCF-7 cells, which we transfected with a full-length NR2F6 cDNA expression plasmid. These studies permitted us to identify palmitoylethanolamide as the only endogenous organic molecule binding NR2F6 with high affinity and reproducibility.
2025-04-15 | E-MTAB-14498 | biostudies-arrayexpress
Project description:Natural killer (NK) cell development and functionality rely on precise regulation by specific transcription factors (TFs). Our study demonstrates that the nuclear orphan receptor NR2F6 represses the expression of the activating receptor NKp46, an established key player in NK cell-mediated cytotoxicity during infection and tumor rejection. Despite normal NK cell development in the bone marrow, germline Nr2f6-deficient mice exhibit impaired terminal maturation of NK cells in the periphery. Short-term NK cell responses to lipopolysaccharide (LPS) activation, independent of NKp46, are subsequently reduced in Nr2f6-deficient mice. Conventional type 1 dendritic cells (cDC1) and macrophage populations are decreased in spleens of Nr2f6-deficient mice, subsequently, IL-15-dependent NK cell priming is limited. Administration of exogenous IL-15 in vitro and as IL-15 complex in vivo can compensate for these deficits, promoting terminal maturation of NK cells in Nr2f6-deficient mice. Subsequent transcriptome analysis reveals significant changes in gene expression profiles of NK cells from IL-15 complex treated Nr2f6-deficient mice, with notable alterations in essential NK genes such as Klrg1, Prdm1, Stat5a, Zeb2, and Prf1. Consequently, Nr2f6-deficient IL-15 complex treated NK cells raise enhanced effector responses of IFNγ, Perforin, and Granzyme B upon ex vivo activation. Of importance, Nr2f6-deficient mice are protected against MHC-I negative B16-F10 melanoma lung metastasis formation, especially with IL-15 complex treatment, indicating the potential of NR2F6 to affect NKp46-dependent NK cell-mediated tumor surveillance. The therapeutic targeting of NR2F6 may be a promising strategy for boosting NKp46-dependent NK-cell-mediated tumor surveillance and metastasis.
2025-02-10 | GSE263734 | GEO
Project description:Role of p300 in regulation of stress-response genes in heart is not clear. Treatment with anti-cancer drug Doxorubicin causes cardiotoxicity through generation of oxidative stress in cardiac myocytes. Loss of p300 enhances cell death and apoptosis in response to Doxorubicin. The objective of this study was to determine if expression of genes regulated by oxidative stress is dependent of presence of p300. Further we investigated if protective effect of p300 against Doxorubicin was due to gene expression effects of p300. We used microarray to compare the transcriptomes of cardiac myocytes transfected with anti-p300 or non-silencing siRNA beforebefore and after exposure to Doxorubicin.
2015-10-01 | GSE42177 | GEO
Project description:Nuclear receptors regulate key functions of mononuclear phagocytes and are critical components of the innate immune system, acting as regulators of organ health and disease. In healthy mice, NR2F6 deficiency alters tissue-resident macrophage populations in the liver, lung, and spleen. In response to Salmonella Typhimurium infection, mice deficient in the nuclear receptor NR2F6 exhibit improved clinical outcomes, characterized by reduced weight loss, bacterial loads in the spleen and liver, and decreased plasma pro-inflammatory cytokines. Despite unchanged basal iron metabolism in the spleen and liver, iron regulatory proteins and the IL-6-hepcidin axis are altered in Nr2f6-deficient mice during Salmonella infection, reducing hypoferremia. Transcriptomic analysis of splenic red pulp macrophages reveals significant alterations of phagocytosis-related genes, including upregulation of Sirpa. In vitro, phagocytosis of red blood cells, regulated by the inhibitory CD47-Sirp axis, and Salmonella Typhimurium phagocytosis is significantly impaired in Nr2f6-deficient splenic macrophages. Blocking Sirp in vitro restores the phagocytic activity of Nr2f6-deficient macrophages to wild-type levels. In vivo, Salmonella Typhimurium loads are partially increased post-infection in anti-Sirp treated Nr2f6-deficient mice. These findings uncover a previously unrecognized role of NR2F6 in host-pathogen interactions, positioning it as a potential therapeutic target for infectious diseases.
2025-07-06 | GSE250198 | GEO
Project description:We used microarrays to characterize the global changes in gene expression in C2C12 cells due to siRNA knockdown of long non-coding RNA H19 Control siRNA or siRNA specific for mouse H19 were transfected into day1 differentiating C2C12 myoblasts in triplicates. 40 H later total RNAs were isolated and subjected with microarray analysis.
2013-09-30 | E-GEOD-49535 | biostudies-arrayexpress
Project description:Analyzing mouse tumor models in vivo, human T cells ex vivo and human lung cancer samples, we provide direct evidence that NR2F6 acts as novel immune checkpoint. Genetic ablation of Nr2f6, particularly in combination with blockade of the established PD-L1 cancer immune checkpoint, efficiently delayed tumor progression and improved survival in experimental mouse models. The target genes deregulated in intratumoral T lymphocytes upon genetic ablation of Nr2f6 alone or together with PD-L1 blockade, revealed multiple advantageous transcriptional alterations for effective tumor rejection. In keeping with the above observation, acute Nr2f6 silencing in both mouse and human T cells induced hyper-responsiveness that established a non-redundant T cell-inhibitory function of NR2F6. Analyzing mouse tumor models in vivo, human T cells ex vivo and human lung cancer samples,
2018-03-14 | GSE111796 | GEO
Project description:Analysis of differentiating C2C12 myoblasts treated with two LSD1 specific inhibitors. We found LSD1 is an important regulator of oxidative phenotypes in skeletal muscle cells. Results provide insight into the molecular mechanisms underlying roles of LSD1 in myocytes.
2018-03-19 | GSE86524 | GEO