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Analyses of mIRNA transcript level following exposure to triptolide

ABSTRACT: Analyses of mirna transcript levels following exposure to the drug triptolide in vitro and prodrug minnelide in xenograft pancreatic tumor mouse models.

ORGANISM(S): Homo sapiens

PROVIDER: GSE46188 | GEO | 2013/11/12

SECONDARY ACCESSION(S): PRJNA198032

REPOSITORIES: GEO

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Analyses of mIRNA transcript level following exposure to triptolide

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

Analyses of mIRNA transcript level following exposure to triptolide

Project description: Not available

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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.

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Dysregulation of lncRNAs and circRNAs in mouse testes after exposure to triptolide

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.

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lncRNA expression profiles in spermatocyte cell line (GC2) after exposure to triptolide and triptonide

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.

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Project description:This study invesitgated the super-enhancer (SE) networks in pancreatic cancer cells and cancer associated fibroblasts (CAFs) as well as the effects of triptolide treatment on the SEs and the expression of the SE associated genes using ChIP-Seq and RNA-Seq.

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The genes affected by Triptolide in activated mouse primary T cells

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.

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