Analyses of mIRNA transcript level following exposure to triptolide
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE46188 | GEO | 2013/11/12
SECONDARY ACCESSION(S): PRJNA198032
REPOSITORIES: GEO
Similar Datasets
Project description:Analyses of mirna transcript levels following exposure to the drug triptolide in vitro and prodrug minnelide in xenograft pancreatic tumor mouse models. Response of pancreatic adenocarcinoma cell lines to minelide in vitro and exposure to its prodrug triptolide in SCID mouse tumors derived from the same cell lines.
2013-11-12 | E-GEOD-46188 | biostudies-arrayexpress
Project description:Analyses of mirna transcript levels following exposure to the drug triptolide in vitro and prodrug minnelide in xenograft pancreatic tumor mouse models. Response of pancreatic adenocarcinoma cell lines to minelide in vitro and exposure to its prodrug triptolide in SCID mouse tumors derived from the same cell lines.
| S-ECPF-GEOD-46188 | biostudies-other
Project description:Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare form of ovarian cancer affecting young women and girls. Survival rates remain poor despite aggressive treatment of these patients with high-dose chemotherapy and radiation. SCCOHT is driven by loss of both SWI/SNF ATPases SMARCA4 and SMARCA2. Loss of SWI/SNF complex activity alters chromatin state, particularly at enhancers, which is believed to be crucial for oncogenesis. Super-enhancers are a distinct subset of enhancer clusters frequently associated with oncogenes in cancer. Here we discovered key distinctions between SWI/SNF binding following SMARCA4 restoration at enhancer vs. super-enhancer sites and characterized putative oncogene expression driven by super-enhancer activity. We found high sensitivity of SCCOHT cell lines to triptolide, a small molecule derived from the naturally occurring "thunder god vine" (Tripterygium wilfordii) that targets the XPB subunit of the transcription factor II H (TFIIH) complex, found at super-enhancers. Triptolide inhibits expression of many super-enhancer associated genes, and in particular, oncogenes. Notably, SALL4 expression, which is high in SCCOHT relative to other ovarian cancers and normal cell types, is significantly decreased following short triptolide treatment. In SCCOHT patient-derived xenograft models, triptolide and its prodrug derivative minnelide are particularly effective in inhibiting tumor growth. These results demonstrate the key oncogenic role of super-enhancer activity following epigenetic dysfunction in SCCOHT, which can be effectively targeted through inhibition of its functional components, such as TFIIH inhibition with triptolide.
2025-01-04 | GSE232831 | GEO
Project description:Pancreatic cancer is characterized by heavy desmoplasia. Triptolide and its water-soluble pro-drug Minnelide are extremely efficient against pancreatic cancer in animal models. However, the effects of triptolide on pancreatic cancer stromal cells are largely unknown. The aim of this project is to indentify potential cellular functions that are affected by triptolide in pancreatic cancer associated fibroblasts.
2016-11-01 | GSE74490 | GEO
Project description:Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare form of ovarian cancer affecting young women and girls. Survival rates remain poor despite aggressive treatment of these patients with high-dose chemotherapy and radiation. SCCOHT is driven by loss of both SWI/SNF ATPases SMARCA4 and SMARCA2. Loss of SWI/SNF complex activity alters chromatin state, particularly at enhancers, which is believed to be crucial for oncogenesis. Super-enhancers are a distinct subset of enhancer clusters frequently associated with oncogenes in cancer. Here we discovered key distinctions between SWI/SNF binding following SMARCA4 restoration at enhancer vs. super-enhancer sites and characterized putative oncogene expression driven by super-enhancer activity. We found high sensitivity of SCCOHT cell lines to triptolide, a small molecule derived from the naturally occurring "thunder god vine" (Tripterygium wilfordii) that targets the XPB subunit of the transcription factor II H (TFIIH) complex, found at super-enhancers. Triptolide inhibits expression of many super-enhancer associated genes, and in particular, oncogenes. Notably, SALL4 expression, which is high in SCCOHT relative to other ovarian cancers and normal cell types, is significantly decreased following short triptolide treatment. In SCCOHT patient-derived xenograft models, triptolide and its prodrug derivative minnelide are particularly effective in inhibiting tumor growth. These results demonstrate the key oncogenic role of super-enhancer activity following epigenetic dysfunction in SCCOHT, which can be effectively targeted through inhibition of its functional components, such as TFIIH inhibition with triptolide.
2025-01-04 | GSE232745 | GEO
Project description:Small cell carcinoma of the ovary-hypercalcemic type (SCCOHT) is a rare form of ovarian cancer affecting young women and girls. Survival rates remain poor despite aggressive treatment of these patients with high-dose chemotherapy and radiation. SCCOHT is driven by loss of both SWI/SNF ATPases SMARCA4 and SMARCA2. Loss of SWI/SNF complex activity alters chromatin state, particularly at enhancers, which is believed to be crucial for oncogenesis. Super-enhancers are a distinct subset of enhancer clusters frequently associated with oncogenes in cancer. Here we discovered key distinctions between SWI/SNF binding following SMARCA4 restoration at enhancer vs. super-enhancer sites and characterized putative oncogene expression driven by super-enhancer activity. We found high sensitivity of SCCOHT cell lines to triptolide, a small molecule derived from the naturally occurring "thunder god vine" (Tripterygium wilfordii) that targets the XPB subunit of the transcription factor II H (TFIIH) complex, found at super-enhancers. Triptolide inhibits expression of many super-enhancer associated genes, and in particular, oncogenes. Notably, SALL4 expression, which is high in SCCOHT relative to other ovarian cancers and normal cell types, is significantly decreased following short triptolide treatment. In SCCOHT patient-derived xenograft models, triptolide and its prodrug derivative minnelide are particularly effective in inhibiting tumor growth. These results demonstrate the key oncogenic role of super-enhancer activity following epigenetic dysfunction in SCCOHT, which can be effectively targeted through inhibition of its functional components, such as TFIIH inhibition with triptolide.
2025-01-04 | GSE232727 | GEO
Project description:Triptolide has been shown to exert various pharmacological effects on systemic autoimmune diseases and cancers. However, its severe toxicity, especially reproduction toxicity, prevents wide clinical use for those people with fertility needs. Noncoding RNAs including lncRNAs and cicrRNAs are regulatory molecules that mediate a wide variety of physiological activities, which are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in triptolide-induced reproduction toxicity is fully unknown. Here, after exposure of mice to triptolide for 35 day, the total RNAs were used to investigate lncRNAs/cicrRNAs/mRNAs expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in triptolide-induced toxicity. The results showed that triptolide significantly decreased the testicular weight, damaged testis and sperm morphology, reduced sperm motility and density. Furthermore, there's a remarkable deformity in sperm head and tail in triptolide-exposed mice. At the transcriptome level, the triptolide-treated mice exhibited aberrant expression profiles for lncRNAs/cicrRNAs/mRNAs, many of them were dysregulated. Gene ontology and pathway analyses revealed that the functions of differentially expressed lncRNA targets, cicrRNAs cognate genes and mRNAs were closely linked with many processes involved in spermatogenesis. Additionally, many newly identified lncRNAs /cicrRNAs displayed inducible expression, suggesting that they might be good candidate markers for triptolide-induced male reproductive toxicity. This study gives us an insight into understanding the reproductive system toxicity of triptolide and reminds us to strengthen the research on increasing efficacy and decreasing toxicity of triptolide.
2020-03-23 | GSE126857 | GEO
Project description:Triptolide or triptonide, major bioactive components isolated from the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF), have been shown to exert various pharmacological effects on systemic autoimmune disease. However, the severe toxicity, especially reproduction toxicity, of triptolide or triptonide prevents wide clinical use for those people with fertility needs. Long noncoding (lnc) RNAs are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in triptolide or triptonide -induced reproduction toxicity is unknown. Here we found that exposure of spermatocyte cell line (GC2) to triptolide or triptonide led to reduction in cell viability and induced cell apoptosis and autophagy. Then the total RNAs of triptolide or triptonide -treated GC2 cells were used to investigate lncRNA expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in triptolide or triptonide-induced toxicity. Gene ontology and pathway analyses showed that the functions of differentially expressed lncRNA targets and mRNAs were closely linked with many processes involved in spermatogenesis.
2022-03-01 | GSE127662 | GEO
Project description:Triptolide possesses immunosuppressive activity and its efficacy is commonly believed to be related to the suppression of T cells. However, the underlying mechanism is still not well documented and most of the previous study adopted tumor cell lines of immune system as model cells in mechanism research, these cells’ signal transduction pathway can not reflect the real situation of immune system. In this study, we investigated the immunosuppressive mechanism of triptolide on T cell activation and proliferation using mouse primary T lymphocytes. These effects were analyzed along with activation of the TCR and AP-1 pathway. We used microarrays to detail the global programme of gene expression underlying stimulation and triptolide treatment. Mouse primary T cells stimulated with anti-CD3/CD28 antibodies treated with triptolide or not treated with triptolide were selected for RNA extraction and hybridization on Affymetrix microarrays.
2012-12-29 | E-GEOD-32315 | biostudies-arrayexpress
Project description:Expression data from treatment of actinomycin D (2.5uM) and triptolide (500 nM) on MCF7 cells for 2, 4 and 6 hours. We used microarrays to explore the mechanism of triptolide action. MCF7 cells were treated with actinomycin D or triptolide for 2, 4 and 6 hours, RNA was extracted and hybridization on Affymetrix microarrays. Data were normalized by RMA.
2011-10-17 | E-GEOD-28662 | biostudies-arrayexpress