Jinfukang induces cellular apoptosis through activation of Fas and DR4 in A549 cells
Ontology highlight
ABSTRACT:
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR894503_1.fastq.gz | Fastqsanger.gz | |||
| ERR894503_2.fastq.gz | Fastqsanger.gz | |||
| ERR894504_1.fastq.gz | Fastqsanger.gz | |||
| ERR894504_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:The traditional Chinese medicine Jinfukang (JFK) has been shown as a valuable drug for the non-small cell lung cancer (NSCLC) patients. Although clinically effective, the underlining mechanism remains unclear. Here, we performed RNA-seq assays for study the antitumor mechanisms of JFK ethanol extract on lung cancer cell line A549.
2016-05-02 | E-MTAB-3592 | biostudies-arrayexpress
Project description:The traditional Chinese medicine Jinfukang (JFK) has been shown as a valuable drug to treat non-small cell lung cancer (NSCLC). Previously, it was reported that JFK-induced epigenetic alteration is involved in anti-lung cancer activity. In the present study, the effect of JFK on lung cancer cell lines was examined with the aim to further understand the underlying mechanisms of JFK-induced anti-lung cancer activity by transcriptome profiling analysis. JFK was observed to decrease lung cancer cell viability and simultaneously induce cellular morphology alteration. Additionally, this causes cell cycle arrest and apoptosis in A549 cells. The present RNA-seq analysis identified 5,281 genes with differential expression (P<0.05). Gene ontology analysis indicated that genes involved in the cell cycle pathway are downregulated, including cyclin-dependent kinase 2, cyclin-dependent kinase 4, cyclin B1 and cyclin A2, and apoptosis-associated genes are upregulated, including Fas, death receptor 4 (DR4), tumor protein P53 binding protein 2 and BCL2 interacting protein 3 like. Particularly, the present results indicate knockdown of Fas and DR4 attenuates JFK-induced apoptosis in A549 cells. Overall, the present study suggests JFK induces cellular apoptosis through activation of Fas and DR4 in A549 cells and provides an insight for understanding the antitumor mechanisms of this Chinese traditional medicine.
| S-EPMC6126349 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF-α and IFN-γ reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF-α and IFN-γ-stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-κB and p38mapk-dependent fashion. Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF-α and IFN-γ to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant. To investigate the mechanism by which TNF-α and IFN-γ reprogram fibroblasts from resistance to sensitivity to Fas-ligation-induce apoptosis, we exposed human primary lung fibroblasts from an IPF patient (FS087) and non-disease control subject (N78) and the human fetal lung fibroblast cell lung (MRC-5) to TNF-α (10 ng/ml) and IFN-γ (50 U/ml) for 36 hr and analyzed changes in their transcriptomes using Affymetrix microarrays.
2011-01-13 | E-GEOD-26594 | biostudies-arrayexpress
Project description:Idiopathic pulmonary fibrosis (IPF) is associated with the accumulation of collagen-secreting fibroblasts and myofibroblasts in the lung parenchyma. Many mechanisms contribute to their accumulation, including resistance to apoptosis. In previous work, we showed that exposure to the pro-inflammatory cytokines, TNF-α and IFN-γ reverses fibroblast resistance to apoptosis. The goal of this study was to investigate the underlying mechanism. Based on an initial interrogation of the transcriptomes of unstimulated and TNF-α and IFN-γ-stimulated primary lung fibroblasts and the lung fibroblast cell line, MRC5, we show here that among Fas-signaling pathway molecules, Fas expression was increased ~6-fold in an NF-κB and p38mapk-dependent fashion. Prevention of the increase in Fas expression using Fas siRNAs blocked the ability of TNF-α and IFN-γ to sensitize fibroblasts to Fas ligation induced-apoptosis; while enforced adenovirus-mediated Fas overexpression was sufficient to overcome basal resistance to Fas-induced apoptosis. Examination of lung tissues from IPF patients revealed low to absent staining of Fas in fibroblastic cells of fibroblast foci. Collectively, these findings suggest that increased expression of Fas is necessary and sufficient to overcome the resistance of lung fibroblasts to Fas-induced apoptosis. They also suggest that approaches aimed at increasing Fas expression by lung fibroblasts and myofibroblasts may be therapeutically relevant.
2011-01-13 | GSE26594 | GEO
Project description:The EwingM-bM-^@M-^Ys sarcoma protein EWS belongs to the TET family (FUS/TLS, EWS, TAF15) of RNA and DNA binding proteins, implicated in DNA transcription, pre-mRNA splicing and maintenance of genomic integrity. Translocations of these genes are characteristic of particular neoplasias, including EwingM-bM-^@M-^Ys sarcoma. To identify physiological RNA targets of EWS, we performed in vivo cross-linking and immunoprecipitation followed by high-throughput RNA sequencing (HITS-CLIP/CLIP-Seq) in HeLa cells. Sequencing identified EWS binding sites characterized by guanosine-rich motifs in nearly 9000 genes, with particular enrichment in exonic regions near 5M-bM-^@M-^Y splice sites. Exon 6 of the Fas/CD95 receptor, which is alternatively spliced to generate isoforms with opposing activities in programmed cell death, was found as a prominent EWS CLIP target, as well as by chromatin-immunoprecipitation (ChIP) and functional analysis. Manipulation of EWS levels and mutation of EWS binding sites led to changes in alternative splicing consistent with EWS promoting exon 6 inclusion and leading to the synthesis of the pro-apoptotic Fas/CD95 isoform. Biochemical characterization of factors associated with FAS exon 6 are consistent with the notion that EWS binds to exonic sequences near the 5M-bM-^@M-^Y splice site and promotes the recruitment of U1snRNP, favoring also recognition of the upstream 3' splice site by U2AF and thus exon definition. Consistent with a role for EWS in the regulation of programmed cell death, cells depleted of EWS show decreased sensitivity to Fas-induced apoptosis. We discuss the potential implications of this novel function of EWS in EwingM-bM-^@M-^Ys sarcoma. CLIP-Seq analysis of EWS, with 2 biological replicates of EWS and one non-specific control
2014-05-21 | E-GEOD-48065 | biostudies-arrayexpress
Project description:The Ewing’s sarcoma protein EWS belongs to the TET family (FUS/TLS, EWS, TAF15) of RNA and DNA binding proteins, implicated in DNA transcription, pre-mRNA splicing and maintenance of genomic integrity. Translocations of these genes are characteristic of particular neoplasias, including Ewing’s sarcoma. To identify physiological RNA targets of EWS, we performed in vivo cross-linking and immunoprecipitation followed by high-throughput RNA sequencing (HITS-CLIP/CLIP-Seq) in HeLa cells. Sequencing identified EWS binding sites characterized by guanosine-rich motifs in nearly 9000 genes, with particular enrichment in exonic regions near 5’ splice sites. Exon 6 of the Fas/CD95 receptor, which is alternatively spliced to generate isoforms with opposing activities in programmed cell death, was found as a prominent EWS CLIP target, as well as by chromatin-immunoprecipitation (ChIP) and functional analysis. Manipulation of EWS levels and mutation of EWS binding sites led to changes in alternative splicing consistent with EWS promoting exon 6 inclusion and leading to the synthesis of the pro-apoptotic Fas/CD95 isoform. Biochemical characterization of factors associated with FAS exon 6 are consistent with the notion that EWS binds to exonic sequences near the 5’ splice site and promotes the recruitment of U1snRNP, favoring also recognition of the upstream 3' splice site by U2AF and thus exon definition. Consistent with a role for EWS in the regulation of programmed cell death, cells depleted of EWS show decreased sensitivity to Fas-induced apoptosis. We discuss the potential implications of this novel function of EWS in Ewing’s sarcoma.
2014-05-21 | GSE48065 | GEO
Project description:c-Jun N-terminal kinase (JNK) plays a pivotal role in the regulation of cancer cell apoptosis. Previous studies have revealed that forkhead transcription factor (Foxo3a) is a critical effector of JNK-mediated tumor suppression. However, it is not clear whether caveolin-1 (CAV1) mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK), which induced Foxo3a translocation into the nucleus, resulting in the upregulation of levels of Bax protein. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas siRNA mediated inhibition of CAV1 downregulated p-JNK, and that JNK inhibition by SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation (p-Foxo3a), which attenuated Foxo3a translocation into the nucleus, indicating caveolin-1 mediated JNK’s regulation of Foxo3a. siRNA mediated inhibition of Foxo3a downregulated levels of Bax protein, attenuated A549 cell apoptosis, indicating that CAV1 mediated JNK/Foxo3a pathway induce the apoptosis of A549 lung cancer cells. Taken, together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation to induce apoptosis in lung cancer cells and support the potential of cordycepin as a therapeutic agent for lung cancer.
2016-05-24 | GSE81727 | GEO
Project description:In this study, we found that CB inhibited ICC cell proliferation and promoted cell apoptosis. By using phosphoproteomics, we found significant changes in the proteome and phosphorylome associated with DNA damage and apoptosis in response to CB treatment. Further investigations demonstrated that CB induced ICC cell apoptosis by activating the ATM/CHK2/p53 signaling pathway and upregulating the expression of Fas, DR4 and DR5. Our results collectively indicate that CB may serve as a potential anti-cholangiocarcinoma drug
2022-06-20 | PXD034717 |
Project description:To exmaine the apoptosis independent function of FAS knockout transcriptome in OSCC cells, we preformed the Affymetrix Human Genome U133 Plus 2.0 Array with CRISPR/Cas9 control or FAS knockout in SAS cells
2023-03-14 | GSE147052 | GEO
Project description:We comprehensively explored Fas expression (protein and mRNA) and function in lymphocyte activation, apoptosis, proliferation and transcriptome, using flow cytometry, [3H]-thymidine incorporation and microarray analysis in PBMC from HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) patients.
2017-02-01 | GSE82160 | GEO