Jinfukang induces cellular apoptosis through activation of Fas and DR4 in A549 cells
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina Hiseq 2000, Illumina HiSeq 2000
ORGANISM(S): Homo sapiens
SUBMITTER: Jun Wu
PROVIDER: E-MTAB-3592 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:Polycomb repressive complexes (PRC) play a critical role during tumorigenesis and development. The histone methyltransferase Enhancer of Zeste homologue 2 (EZH2), as a core component of PRC2, is frequently overexpressed in a wide variety of cancers. EZH2-mediated gene silencing contributes to carcinogenesis. To further the understanding of the EZH2 biology in gastric cancer, here we performed transcriptome analyses and identified EZH2-responsive genes upon EZH2 knockdown by RNA-seq.
2015-11-07 | E-MTAB-3227 | 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:We report the application of next-generation sequencing technology for transcription profile analysis of S. cerevisiae strains with different genetic background. By combining the whole genome sequence of these strains, we sought to explore the effects of genome mutations on the transcription diversities. Comparsion of transcription profiles in S. cerevisiae Chinese rice wine strain with laboratory strain
2014-06-16 | E-GEOD-54433 | biostudies-arrayexpress
Project description:In this study,we demonstrated the transcription factor EGR1 is activated by TCM YYJD and such activation mediated YYJD-induced apoptosis in lung cancer cells and provided a novel insight to understand the anti-tumor mechanism of Chinese herb YYJD.
2018-11-01 | E-MTAB-7236 | biostudies-arrayexpress
Project description:In this study,we demonstrated the transcription factor EGR1 is activated by TCM YYJD and such activation mediated YYJD-induced apoptosis in lung cancer cells and provided a novel insight to understand the anti-tumor mechanism of Chinese herb YYJD.
2018-11-01 | E-MTAB-7237 | biostudies-arrayexpress
Project description:Using RNA-seq to identify genes regulated by dCas9-KRAB mediated enhancer repression in NCI-H2009 lung adenocarcinoma cells NCI-H2009 cells were first transfected with dCas9-KRAB fusion and subsequently transfected with no guide RNA (Empty), a guide RNA that has no target in the human genome (Dummy), and two separate guide RNAs (e3 #1 and e3 #2) recognizing the enhancer region of our study.
2015-10-26 | E-GEOD-72001 | biostudies-arrayexpress
Project description:Fas ligand (FasL), an apoptosis-inducing member of the TNF cytokine family, and its receptor Fas are critical for the shutdown of chronic immune responses and prevention of autoimmunity. Accordingly, mutations in their genes cause severe lymphadenopathy and autoimmune disease in mice and humans. FasL function is regulated by deposition in the plasma membrane and metalloprotease-mediated shedding. Here we generated gene-targeted mice that selectively lack either secreted FasL (sFasL) or membrane-bound FasL (mFasL) to resolve which of these forms is required for cell killing and to explore their hypothesized non-apoptotic activities. Mice lacking sFasL (FasL(Deltas/Deltas)) appeared normal and their T cells readily killed target cells, whereas T cells lacking mFasL (FasL(Deltam/Deltam)) could not kill cells through Fas activation. FasL(Deltam/Deltam) mice developed lymphadenopathy and hyper-gammaglobulinaemia, similar to FasL(gld/gld) mice, which express a mutant form of FasL that cannot bind Fas, but surprisingly, FasL(Deltam/Deltam) mice (on a C57BL/6 background) succumbed to systemic lupus erythematosus (SLE)-like autoimmune kidney destruction and histiocytic sarcoma, diseases that occur only rarely and much later in FasL(gld/gld) mice. These results demonstrate that mFasL is essential for cytotoxic activity and constitutes the guardian against lymphadenopathy, autoimmunity and cancer, whereas excess sFasL appears to promote autoimmunity and tumorigenesis through non-apoptotic activities.
| S-EPMC2785124 | biostudies-literature
Project description:Targeted inhibition of mitochondrial oxidative phosphorylation (OXPHOS) complex generation is an emerging and promising cancer treatment strategy, but limited targets and specific inhibitors have been reported. Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is an atypical RNA-binding protein that regulates the stability of all 13 mitochondrial DNA-encoded mRNA (mt-mRNA) and thus participates in the synthesis of the OXPHOS complex. LRPPRC is also a prospective therapeutic target for lung adenocarcinoma, serving as a promising target for OXPHOS inhibition. In this study, we identified Demethylzeylasteral (T-96), a small molecule extracted from the Chinese herb Tripterygium wilfordii Hook. f., as a novel inhibitor of LRPPRC. T-96 directly bound to the RNA-binding domain of LRPPRC, inhibiting its interaction with mt-mRNA. This led to instability in both mt-mRNA and LRPPRC protein. Treatment with T-96 significantly reduced the mRNA and protein levels of the OXPHOS complex. As a consequence of LRPPRC inhibition, T-96 treatment induced a defect in the synthesis of the OXPHOS complex, inhibiting mitochondrial aerobic respiration and ATP synthesis. Moreover, T-96 exhibited potent antitumor activity for lung adenocarcinoma in vitro and in vivo, and the antitumor effect of T-96 was dependent on LRPPRC expression. In conclusion, this study not only identified the first traditional Chinese medicine monomer inhibitor against OXPHOS complex biosynthesis as well as a novel target of Demethylzeylasteral, but also shed light on the unique antitumor mechanism of bioactive compounds derived from traditional Chinese medicine.
2024-10-09 | GSE279114 | GEO