Reduced cancer incidence has been reported among type II diabetics treated with metformin. Metformin exhibits anti-proliferative and anti-neoplastic effects associated with inhibition of mTORC1, but the mechanisms are poorly understood. We provide the first genome-wide analysis of translational targets of canonical mTOR inhibitors (rapamycin and PP242) and metformin, revealing that metformin controls gene expression at the level of mRNA translation to an extent comparable to that of canonical mTOR inhibitors. Importantly, metformin's anti-proliferative activity can be explained by selective translational suppression of mRNAs encoding cell cycle regulators via the mTORC1/4E-BP pathway. Thus, metformin selectively inhibits mRNA translation of encoded proteins that promote neoplastic proliferation, motivating further studies of this compound and related biguanides in cancer prevention and treatment.
Distinct perturbation of the translatome by the antidiabetic drug metformin.
Cell line, Treatment
View SamplesMaternal smoking has a severe negative effect on all stages of pregnancy that in consequence impairs fetal growth and development. Tobacco smoke-related defects are well established at the clinical level; however, little is known about molecular mechanisms underlying these pathological conditions. We thus employed a genomic approach to determine transcriptome alterations induced by maternal smoking in pregnancy. We assayed gene expression profiles in peripheral blood (M) leukocytes and placentas (PL) of pregnant smokers and those without significant exposure, and in cord blood (D) leukocytes of their babies. Comparative analyses defined significant deregulation of 193 genes in M cells, 329 genes in placentas, and 49 genes in D cells of smokers. These genes were mainly involved in xenobiotic metabolism, oxidative stress, inflammation, immunity, hematopoiesis, trophoblast differentiation, and vascularization. Functional annotation of the deregulated genes outlined processes and pathways affected by tobacco smoke. In smoker newborns, we identified several deregulated pathways associated with autoimmune diseases. The study demonstrates a limited ability of placenta to modulate toxic effects of maternal tobacco use at the gene expression level.
Transcriptome alterations in maternal and fetal cells induced by tobacco smoke.
Age, Specimen part, Subject
View SamplesPassive smoke intake by pregnant women may have detrimental effects such as spontaneous abortion, lower birth weight, stillbirth, and reduced infant lung function. To extend our knowledge on molecular effects of tobacco smoke exposure in pregnancy, we analyzed transcriptome alterations in passive smokers (PS) and compared them to those in active smokers (AS). Using Illumina Expression Beadchip with 24,526 transcript probes, gene expression patterns were assayed in placentas from PS (N=25) exposed to environmental tobacco smoke (ETS) throughout pregnancy and non-exposed (NS) counterparts (N=35), and in cord blood cells from their newborns. The ETS exposure was evaluated by questionnaire disclosure and cotinine measurement in maternal and cord bloods. A total of 196 genes were significantly deregulated in placentas of PS compared to NS. These genes were primary associated with extracellular matrix, apoptosis, blood clotting, response to stress, embryonic morphogenesis, and lipid metabolism. Cord blood of newborns of PS displayed differential expression of 116 genes encoding mainly neuronal factors, regulators of immunologic response, and protooncogenes. Gene ontology analyses highlighted some important biological processes that might be associated with placental insufficiency and fetal growth restriction in PS, such as fatty acid catabolism, coagulation, regulation of growth, and response to steroid hormone stimulus. The study demonstrates that even low dose exposure to ETS during pregnancy leads to the significant deregulation of transcriptional regulation in placental and fetal cells. The data suggest the effect of ETS on the fetus is primary indirect, mediated via deregulation of placental functions. Comparison of PS and AS indicated that ETS exposure and active smoking in pregnancy partly employ the same molecular mechanisms.
Deregulation of gene expression induced by environmental tobacco smoke exposure in pregnancy.
Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
No sample metadata fields
View SamplesA huge number of microorganisms are colonized in human gut and the balance of their composition is closely related to human health. Recently, many probiotics such as bifidobacteria or lactobacilli have been introduced in our life as effective agents. However, we have not well understood their beneficial mechanisms including host-bacterial crosstalk. Accordingly, we took advantage of the protective mechanisms of probiotics against lethal infection of enterohemorrhagic Escherichia coli O157:H7 in murine gnotobiote model system
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
No sample metadata fields
View SamplesA huge number of microorganisms are colonized in human gut and the balance of their composition is closely related to human health. Recently, many probiotics such as bifidobacteria or lactobacilli have been introduced in our life as effective agents. However, we have not well understood their beneficial mechanisms including host-bacterial crosstalk To analyze the differences of gene expression between BA- or BL-associated murine colonic epithelium, we performed comparative transcriptomic analysis.
Bifidobacteria can protect from enteropathogenic infection through production of acetate.
No sample metadata fields
View SamplesCidofovir is an acyclic nucleoside phosphonate with strong antiviral activity against a broad spectrum of DNA viruses. Although it has previously been shown that cidofovir exerts an antiproliferative effect on HPV positive cells by the induction of apoptosis, the exact mechanism of action remains to be unraveled. In order to study the activity of cidofovir against HPV, gene expression profiling was performed in cidofovir-treated and cidofovir-resistant HeLa, HaCaT, and PHK cells by means of microarrays (HG-U133 Plus 2, Affymetrix).
Cidofovir selectivity is based on the different response of normal and cancer cells to DNA damage.
Specimen part, Disease, Cell line
View SamplesMost cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC).
Pancreatic cancer circulating tumour cells express a cell motility gene signature that predicts survival after surgery.
Sex, Age, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Specimen part
View SamplesTo elucidate the mechamisms of colonic Treg cell induction by microbial metabolite(s), chroloform-resistant bacteria (CRB)-associated mice was developed and given low-fiber diet (LFD) and high-fiber diet (HFD). The colonic epithelial cells were isolated and gene expression profiles were analyzed by GeneChip.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Sex, Age, Specimen part, Treatment
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