M12-28: MRX34 Biomarker study in animals bearing HuH7 orthotopic liver tumors [Affymetrix]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE58800 | GEO | 2014/11/05
SECONDARY ACCESSION(S): PRJNA253528
REPOSITORIES: GEO
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Project description:To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34 HuH7 cells were surgically implanted into the livers of Nod/Scid mice and allow to grow for multiple weeks. Once serum AFP levels reached levels consistent with tumor growth of ~80-100 mg, animals were subjected to a single IV injection of MRX34. Twenty-four hours later animals were sacrificed, tumors resected and RNA isolated for subsequent microarray analysis.
2014-11-05 | E-GEOD-58800 | biostudies-arrayexpress
Project description:To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34
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Project description:To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34 Hep3B cells were surgically implanted into the livers of Nod/Scid mice and allow to grow for multiple weeks. Once serum AFP levels reached levels consistent with tumor growth of ~80-100 mg, animals were subjected to a single IV injection of MRX34. Twenty-four hours later animals were sacrificed, tumors resected and RNA isolated for subsequent microarray analysis.
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Project description:This SuperSeries is composed of the SubSeries listed below.
2014-11-05 | GSE58893 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-11-05 | E-GEOD-58893 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs or miRs) are small, noncoding RNAs that are implicated in the regulation of nearly all biological processes. Global miRNA biogenesis is altered in many cancers and RNA-binding proteins (RBPs) have been shown to play a role in this process, presenting a promising avenue for targeting miRNA dysregulation in disease. miR-34a exhibits tumor-suppressive functions by targeting cell cycle regulators CDK4/6 and anti-apoptotic factor Bcl-2, among other regulatory pathways such as Wnt, TGF-, and Notch signaling. Many cancers show downregulation or loss of miR-34a, and synthetic miR-34a supplementation has been shown to inhibit tumor growth in vivo; however, the post-transcriptional mechanisms by which miR-34a is lost in cancer are not entirely understood. Here, we have used a proteomics-mediated approach to identify Squamous cell carcinoma antigen recognized by T-cells 3 (SART3) as a putative pre-miR-34a-binding protein. SART3 is a spliceosome recycling factor and nuclear RBP with no previously reported role in miRNA regulation. We demonstrate that SART3 binds pre-miR-34a with specificity over pre-let-7d and begin to elucidate a new functional role for this protein in non-small lung cancer cells. Overexpression of SART3 led to increased miR-34a levels, downregulation of the miR-34a target genes CDK4 and CDK6, and cell cycle arrest in the G1 phase. In vitro binding studies showed that the RNA-recognition motifs within the SART3 sequence are responsible for selective pre-miR-34a binding. Collectively, our results present evidence for an influential role of SART3 in miR-34a biogenesis and cell cycle progression.
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Project description:Anorexia is frequently observed during cancer and associated with increased morbidity and mortality. Our previous work has shown the presence of transcription factors in the hypothalamus of anorectic tumor-bearing rats. The aim of the present study was, therefore, to assess expression of neuropeptides, neurotransmitter-synthesizing enzymes and receptors in this structure. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 15% reduction in food intake and 10% lower body weight when the tumor represented 1-2% of body mass. Real-time PCR showed that tumor-bearing rats did not display the increase in hypothalamic agouti-related peptide mRNA observed in food-restricted weight-matched animals. These findings indicate that blunted hypothalamic AgRp mRNA expression underlies cancer-associated anorexia.
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Project description:Altered by defects in p53, epigenetic silencing, and genomic loss, the microRNA miR-34a represents one of the most clinically relevant tumor-suppressive microRNAs. Without question, a striking number of patients with cancer would benefit from miR-34a replacement, if poor miR-34a stability, non-specific delivery, and delivery-associated toxicity could be overcome. Here, we highlight a fully modified version of miR-34a (FM-miR-34a) that overcomes these hurdles when conjugated to a synthetically simplistic ligand. FM-miR-34a is orders of magnitude more stable than a partially modified version, without compromising its activity, leading to stronger repression of a greater number of miR-34a targets. FM-miR-34a potently inhibited proliferation and invasion, and induced sustained downregulation of endogenous target genes for >120 hours following in vivo delivery. In vivo targeting was achieved through conjugating FM-miR-34a conjugated to folate (FM-FolamiR-34a), which inhibited tumor growth leading to complete cures in some mice. These results have the ability to revitalize miR-34a as an anti-cancer agent, providing a strong rationale for clinical testing.
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Project description:Anorexia is frequently observed during cancer and associated with increased morbidity and mortality. Our previous work has shown the presence of transcription factors in the ventral striatum of anorectic tumor-bearing rats. The aim of the present study was, therefore, to assess expression of neuropeptides, neurotransmitter-synthesizing enzymes and receptors in this structure. Morris hepatoma 7777 cells injected subcutaneously in Buffalo rats provoked a 15% reduction in food intake and 10% lower body weight when the tumor represented 1-2% of body mass. Mircorarrays and real-time PCR revealed increased ventral striatal prostaglandin D synthase expression in food-restricted animals compared to anorectic tumor-bearing rats. These findings indicate that reduced ventral striatal prostaglandin D synthesis underlies cancer-associated anorexia.
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Project description:The aim of this study was to investigate the inhibitory effect of TSU68, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRβ) and fibroblast growth factor receptor 1 (FGFR1), on colon cancer liver metastasis and to test the hypothesis that TSU68 modulates the microenvironment in the liver before the formation of metastasis. Experiment Overall Design: The human colon cancer TK-4 was implanted orthotopically into cecal walls of 6-week-old male BALB/c nu/nu mice (Clea Japan, Tokyo, Japan). The animals were treated with TSU68 (400 mg/kg/day, twice-daily, p.o.) or vehicle from 7 days after orthotopic implantation. After one week of drug administration, livers were removed and total RNA was extracted. Experiment Overall Design: We established four different groups of mice; non-tumor-bearing and treated with vehicle alone (NT-Co), non-tumor-bearing and treated with TSU68 (NT-TSU), tumor-bearing and treated with vehicle (T-Co), and tumor-bearing and treated with TSU68 (T-TSU). NT-Co, T-Co and T-TSU group were applied to microarray analysis.
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