A key netwrok hub gene GRN confers chemo resistance in H2081 SCLC cells.
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ABSTRACT:
PROVIDER: PRJNA1026975 | ENA |
REPOSITORIES: ENA
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Project description:NCI-H2081 is a cisplatin sensitive cell line. We over-expressed GRN protein in the cell to test whether GRN expression confers chemo-resistance into the cells. GRN over-expression is sufficient to confer chemo-resistance to small cell lung cancer (NCI-H2081). Genes differentially expressed in GRN-overexpressed cells compared to control cells were identified by DESeq2 (FDR < 0.01). Down-regulated genes were enriched for neuroendocrine signatures including ASCL1.
2025-02-12 | GSE245123 | GEO
Project description:Panicum virgatum GRN Resequencing genome sequencing
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Project description:Even though small cell lung cancer (SCLC) has entered the age of broad genomic analysis, platinum-based chemotherapy remains the standard care for SCLC. Topotecan is the only approved agent for recurrent or progressive SCLC (1). In the absence of well-defined genomic biomarkers, clinical efficacy signals in genomically distinct subsets of SCLC could have been missed. Serine/Arginine Splicing Factor 1 (SRSF1) is a member of SR protein family. The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation (2). Whole exome and transcriptome sequencing of primary tumor SCLC from 99 Chinese patients has identified SRSF1 DNA amplification and mRNA over-expression which predicts poor survival in Chinese SCLC patients. In vitro and in vivo studies have demonstrated that SRSF1 is essential for tumorigenecity of SCLC and plays a key role in DNA repair and chemo-sensitivity. We did RNAseq on 79 small cell lung cancer patients' tumor sample and 7 normal lung tissue. We normalized the RNAseq data and did differential expression analysis. The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation.
2016-02-10 | E-GEOD-60052 | biostudies-arrayexpress
Project description:Even though small cell lung cancer (SCLC) has entered the age of broad genomic analysis, platinum-based chemotherapy remains the standard care for SCLC. Topotecan is the only approved agent for recurrent or progressive SCLC (1). In the absence of well-defined genomic biomarkers, clinical efficacy signals in genomically distinct subsets of SCLC could have been missed. Serine/Arginine Splicing Factor 1 (SRSF1) is a member of SR protein family. The deleterious consequences of overexpression of the SRSF1 proto-oncogene in human cancers suggest that there are complex mechanisms and pathways underlying SRSF1-mediated transformation (2). Whole exome and transcriptome sequencing of primary tumor SCLC from 99 Chinese patients has identified SRSF1 DNA amplification and mRNA over-expression which predicts poor survival in Chinese SCLC patients. In vitro and in vivo studies have demonstrated that SRSF1 is essential for tumorigenecity of SCLC and plays a key role in DNA repair and chemo-sensitivity.
2016-02-10 | GSE60052 | GEO
Project description:Frontotemporal dementia is the second most common form of presenile dementia and autosomal dominant inheritance is present in 20-30% of cases, with mutations in granulin (GRN) as a major cause. The exact pathophysiological mechanism by which GRN mutations lead to neurodegeneration is poorly understood. We aimed to identify novel cerebrospinal fluid (CSF) biomarkers in GRN-associated frontotemporal dementia using shotgun proteomics. We included CSF from presymptomatic and symptomatic GRN mutation carriers and healthy non-carriers (controls). We validated our discovery proteomics results in a large international cohort of GRN-mutation carriers and other forms of genetic FTD (C9orf72- and MAPT-mutation carriers) by parallel reaction monitoring.
2019-04-30 | PXD012178 | Pride
Project description:Frontotemporal dementia is the second most common form of presenile dementia and autosomal dominant inheritance is present in 20-30% of cases, with mutations in granulin (GRN) as a major cause. The exact pathophysiological mechanism by which GRN mutations lead to neurodegeneration is poorly understood. We aimed to identify novel cerebrospinal fluid (CSF) biomarkers in GRN-associated frontotemporal dementia using shotgun proteomics. We included CSF from presymptomatic and symptomatic GRN mutation carriers and healthy non-carriers (controls). We validated our discovery proteomics results in a large international cohort of GRN-mutation carriers and other forms of genetic FTD (C9orf72- and MAPT-mutation carriers) by parallel reaction monitoring.
2019-04-29 | PXD012179 | Pride
Project description:Little has been known about the genome-wide methylation frameworks of the chemo-resistant cells of SCLC currently, which might provide prospective layouts to discover the genes and the signal pathways related with chemo-resistance of SCLC. Thus, this research reported for the first time the genome-wide abnormal methylation pattern of chemo-resistant H446/DDP cells of human SCLC induced by the cisplatin
2022-11-20 | GSE140743 | GEO
Project description:Using unbiased kinase profiling, we identified protein kinase A (PKA) as an active kinase in small cell lung cancer (SCLC). Inhibition of PKA activity genetically, or pharmacologically by activation of the PP2A phosphatase, inhibits SCLC expansion in culture and in vivo. Conversely, GNAS (G-protein α subunit), a PKA activator that is genetically activated in a small subset of human SCLC, promotes SCLC development. Phosphoproteomic analyses identified many new PKA substrates and mechanisms of action. In particular, PKA activity is required for the propagation of SCLC cancer stem cells in transplantation studies. Broad proteomic analysis of recalcitrant cancers has the potential to uncover novel targetable signaling networks, such as the GNAS/PKA/PP2A axis in SCLC.
2020-06-17 | PXD018209 | Pride
Project description:RNAseq of SCLC cell line H1155 with PAX5.knocked out. The goals of this study are to identify the function of PAX5 in SCLC.
2021-01-31 | GSE135439 | GEO
Project description:Haploinsufficiency of GRN causes frontotemporal dementia (FTD). The GRN locus produces progranulin (PGRN), which is cleaved to lysosomal granulin polypeptides. The function of lysosomal granulins and why their absence causes neurodegeneration are unclear. Here we discover that PGRN-deficient human cells and murine brains, as well as human frontal lobes from GRN-mutation FTD patients have increased levels of gangliosides, glycosphingolipids that contain sialic acid. In these cells and tissues, levels of lysosomal enzymes that catabolize gangliosides were normal, but levels of bis(monoacylglycero)phosphates (BMP), lipids required for ganglioside catabolism, were reduced with PGRN deficiency. Our findings indicate that granulins are required to maintain BMP levels to support ganglioside catabolism, and that PGRN deficiency in lysosomes leads to gangliosidosis. Lysosomal ganglioside accumulation may contribute to neuroinflammation and neurodegeneration susceptibility observed in FTD due to PGRN deficiency and other neurodegenerative diseases.
2022-09-18 | PXD035889 | Pride