Genome-wide analysis of rats' mRNA profile after knocking down PIWIL1 in embryonic cultured neurons.
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Pingping Zhao
PROVIDER: E-GEOD-48236 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We have demonstrated that PIWIL1 can regulate neuronal radial migration during corticogenesis. In order to explore the mechanism, we carried out high-throughtput sequencing (mRNA profile) to define downstream target of PIWIL during the process of neuronal migration. And we found the expression level of several microtubule-associated proteins decreased after downregulation of PIWIL1. Therefore, PIWIL1 plays an important role in neuronal migration by regulating the expression microtubule-associated proteins (such as Map1B, Map2, Tau) .
2016-06-22 | GSE48236 | GEO
Project description:Human brain development is a complex process involving neural proliferation, differentiation, and migration which are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing(RNA-Seq) dataset, we identified synaptotagmin-like 3(SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibited high activity but low expression in both early developmental human cortex and human embryonic stem cell(hESC)-derived neurons. Knockout of SYTL3(SYTL3 -KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promoted neuronal migration. Besides, SYTL3-KO caused an abnormal distribution of deep-layer neurons in brain organoids and reduced presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrated that SYTL3-KO- accelerated neuronal migration was modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identified SYTL3 as a novel regulator of cortical neuronal migration in human and mouse developing brains.
2021-02-07 | E-MTAB-10058 | biostudies-arrayexpress
Project description:The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). Proteomic and validation immunohistochemical analyses revealed that α-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery. We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxaneâbased therapy. Tumor tissues from pretreatment needle biopsies from patients enrolled on a paclitaxel/radiation clinical trial were laser capture microdissected for RNA extraction and hybridization to Affymetrix microarrays. We analyzed one array (sample A) from duplicate samples from each patient. 14 subject, 2 replicates each.
2010-06-23 | E-GEOD-22513 | biostudies-arrayexpress
Project description:The purpose of this study was to identify molecular markers of pathologic response to neoadjuvant paclitaxel/radiation treatment, protein and gene expression profiling were done on pretreatment biopsies. Patients with high-risk, operable breast cancer were treated with three cycles of paclitaxel followed by concurrent paclitaxel/radiation. Tumor tissue from pretreatment biopsies was obtained from 19 of the 38 patients enrolled in the study. Protein and gene expression profiling were done on serial sections of the biopsies from patients that achieved a pathologic complete response (pCR) and compared to those with residual disease, non-pCR (NR). Proteomic and validation immunohistochemical analyses revealed that α-defensins (DEFA) were overexpressed in tumors from patients with a pCR. Gene expression analysis revealed that MAP2, a microtubule-associated protein, had significantly higher levels of expression in patients achieving a pCR. Elevation of MAP2 in breast cancer cell lines led to increased paclitaxel sensitivity. Furthermore, expression of genes that are associated with the basal-like, triple-negative phenotype were enriched in tumors from patients with a pCR. Analysis of a larger panel of tumors from patients receiving presurgical taxane-based treatment showed that DEFA and MAP2 expression as well as histologic features of inflammation were all statistically associated with response to therapy at the time of surgery. We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane–based therapy.
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Project description:<p><strong>INTRODUCTION:</strong> Neuronal activity regulated by synaptic communication exerts an important role in tumorigenesis and progression in brain tumors. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function ‘vesicle’ about synaptic connectivity were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), was found to have discrepant expression levels in neuropathies. However, the specific mechanism and prognostic value of SNAP25 during glioma progression remain unclear. </p><p><strong>METHODS:</strong> Using RNA sequencing data from The Cancer Genome Atlas (TCGA) database, the differential synaptosis-related genes between LGG and GBM were identified as highly correlated. Cox proportional hazards regression analysis and survival analysis indicated that the candidate gene SNAP25 could differentiate the outcome of low- and high-risk patients, and the Chinese Glioma Genome Atlas (CGGA) cohort was used for validation of the data set. RT-qPCR, western blot, and immunohistochemistry assays were performed to examine the expression level of SNAP25 in glioma cells and samples. Functional assays were performed to identify the effects of SNAP25 knockdown and overexpression on cell viability, migration, and invasion. Then, an immunofluorescence assay of the xenograft tissue was applied to evaluate the expression of the neuronal dendron formation marker-MAP2. Liquid chromatography-high re solution mass spectrometry (LC-MS)-based metabolomics approach was presented for identifying crucial metabolic disturbances in glioma cells. In situ mouse xenograft model was used to investigate the role of SNAP25 in vivo.</p><p><strong>RESULTS:</strong> SNAP25 was down expressed in glioma tissues and cell lines and low-level SNAP25 indicated an unfavorable prognosis of glioma patients. SNAP25 inhibited cell proliferation, migration, invasion and fostered glutamate metabolism of glioma cells, exerting a tumor suppressor role. SNAP25 overexpression expressed lower expression of MAP2, indicating poor neuronal plasticity and connectivity. SNAP25 could interact with glutaminase（GLS）and GLS knockdown could rescue the anti-tumor effect of SNAP25 in glioma cells. Moreover, upregulation of SNAP25 also decreased tumor volume and prolonged the overall survival (OS) of the xenograft mouse.</p><p><strong>CONCLUSION:</strong> SNAP25 inhibited carcinogenesis of glioma via sponging glutamate metabolism by regulating GLS expression, as well as inhibiting dendritic formation, which could be considered as a molecular target for glioma diagnosis and therapy.</p>
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Project description:In contrast to the acute METH-induced transcriptional changes, chronic METH administration produces differential changes in IEG responses and blunts the striatal effects of a single METH injection (McCoy et al., 2011). These observations suggested that chromic METH might have caused changes in the molecular machinery that controls the acute effects of the drug. Gene transcription is regulated by complex interactions of transcription factors with regulatory elements [14,15]. During resting states, DNA is compacted in a way that interferes with the binding of transcription factors whereas DNA becomes more accessible during activation of cells by various stimuli [16]. DNA is indeed packaged into chromatin whose fundamental subunit, the nucleosome, is made of 4 core histones, histones H2A, H2B, H3, and H4 that form an octomer (2 of each histone) surrounded by 146 bp of DNA [17]. The N-tails of histones possess lysine residues that can be reversibly acetylated or deacetylated by several histone acetyltransferases (HATs) or by histone deacetylases (HDACs), respectively [18,19]. These changes promote alterations in gene expression by modifying chromatin conformation and enabling or inhibiting recruitment of regulatory factors onto DNA sequences [20]. Herein, we report that the acute, but not the chronic, transcriptional effects of METH are mediated, for the most part, by increased DNA binding of histone H4 acetylated at lysine 5 (H4K5ac). These results suggest that other factors, including histone and/or DNA methylation, might play a more important role in mediating the molecular effects of chronic METH exposure. 18 samples pooled as SS (4), SM (3), MS (3), MM (4), INPUT (4): SS Saline pretreatment then saline treatment SM Saline pretreatment then METH treatment MS METH pretreatment then saline treatment MM METH pretreatment then METH treatment untreated
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