Search results for " Regulation"
showing 10 items of 3187 documents
BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.
2016
Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromat…
A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype
2016
Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the impor…
NUPR1, a new target in liver cancer: implication in controlling cell growth, migration, invasion and sorafenib resistance
2016
AbstractSorafenib, an oral multikinase inhibitor, is the only approved agent for the treatment of advanced hepatocellular carcinoma (HCC). However, its benefits are modest, and as its mechanisms of action remain elusive, a better understanding of its anticancer effects is needed. Based on our previous study results, we investigated here the implication of the nuclear protein 1 (NUPR1) in HCC and its role in sorafenib treatment. NUPR1 is a stress-inducible protein that is overexpressed in various malignancies, but its role in HCC is not yet fully understood. We found that NUPR1 expression was significantly higher in primary human HCC samples than in the normal liver. Knockdown of NUPR1 signi…
Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study.
2015
Smoking increases the risk of many diseases and could act through changes in DNA methylation patterns. The aims of this study were to determine the association between smoking and DNA methylation throughout the genome at cytosine-phosphate-guanine (CpG) site level and genomic regions. A discovery cross-sectional epigenome-wide association study nested in the follow-up of the REGICOR cohort was designed and included 645 individuals. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Smoking status was self-reported using a standardized questionnaire. We identified 66 differentially methylated CpG sites associated with smoking, located in 38 genes. In most of …
Imatinib spares cKit-expressing prostate neuroendocrine tumors, whereas kills seminal vesicle epithelial-stromal tumors by targeting PDGFR-β
2017
Abstract Prostate cancer is a leading cause of cancer-related death in males worldwide. Indeed, advanced and metastatic disease characterized by androgen resistance and often associated with neuroendocrine (NE) differentiation remains incurable. Using the spontaneous prostate cancer TRAMP model, we have shown that mast cells (MCs) support in vivo the growth of prostate adenocarcinoma, whereas their genetic or pharmacologic targeting favors prostate NE cancer arousal. Aiming at simultaneously targeting prostate NE tumor cells and MCs, both expressing the cKit tyrosine kinase receptor, we have tested the therapeutic effect of imatinib in TRAMP mice. Imatinib-treated TRAMP mice experience a pa…
Rhythmic Regulation of Photoreceptor and RPE Genes Important for Vision and Genetically Associated With Severe Retinal Diseases.
2018
Purpose The aim of the present study was to identify candidate genes for mediating daily adjustment of vision. Methods Genes important for vision and genetically associated with severe retinal diseases were tested for 24-hour rhythms in transcript levels in neuronal retina, microdissected photoreceptors, photoreceptor-related pinealocytes, and retinal pigment epithelium-choroid (RPE-choroid) complex by using quantitative PCR. Results Photoreceptors of wildtype mice display circadian clock-dependent regulation of visual arrestins (Arr1, Arr4) and the visual cycle gene Rdh12, whereas cells of the RPE-choroid exhibit light-dependent regulation of the visual cycle key genes Lrat, Rpe65, and Rdh…
The role of myoglobin in epithelial cancers: Insights from transcriptomics
2019
The muscle-associated respiratory protein myoglobin (MB) is expressed in multiple types of cancer, including breast and prostate tumors. In Kaplan-Meier analyses of the two tumor types, MB positivity is associated with favorable prognoses. Despite its well-characterized function in myocytes, the role of MB in cancer remains unclear. To study the impact of endogenous MB expression, small interfering RNA MB-knockdown cells were engineered using breast, prostate and colon cancer cell lines (MDA-MB468, LNCaP, DLD-1), and their transcriptomes were investigated using RNA-Seq at different oxygen levels. In MB-positive cells, increased expression of glycolytic genes was observed, which was possibly…
Regulation of PDE5 expression in human aorta and thoracic aortic aneurysms
2019
AbstractAneurysms and dissections affecting thoracic aorta are associated with smooth muscle cell (SMC) dysfunction. NO/cGMP signaling pathway in smooth muscle cells has been shown to be affected in sporadic thoracic aortic aneurysms. We analyzed the mRNA levels of PDE5, a cGMP-hydrolyzing enzyme highly expressed in aortic SMCs, that regulates arterious vascular tone by lowering cGMP levels. We found that aortic tissue obtained from Marfan, tricuspid and bicuspid thoracic aneurysms expressed lower levels of PDE5 mRNA compared to control aortas. In particular, we found that affected aortas showed lower levels of all the PDE5A isoforms, compared to control aortas. Transfection of vascular SMC…
Cohesin-dependent regulation of gene expression during differentiation is lost in cohesin-mutated myeloid malignancies.
2019
Cohesin complex disruption alters gene expression, and cohesin mutations are common in myeloid neoplasia, suggesting a critical role in hematopoiesis. Here, we explore cohesin dynamics and regulation of hematopoietic stem cell homeostasis and differentiation. Cohesin binding increases at active regulatory elements only during erythroid differentiation. Prior binding of the repressive Ets transcription factor Etv6 predicts cohesin binding at these elements and Etv6 interacts with cohesin at chromatin. Depletion of cohesin severely impairs erythroid differentiation, particularly at Etv6-prebound loci, but augments self-renewal programs. Together with corroborative findings in acute myeloid le…
Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation
2018
Summary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and “toxic” gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function …