Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA316223 | ENA |
REPOSITORIES: ENA
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Project description:Carbaryl (1-naphthyl-methylcarbamate), a broad-spectrum insecticide, has recently been associated with the development of cutaneous melanoma in an epidemiological cohort study with U.S. farm workers also exposed to ultraviolet radiation, which is known to be the main etiologic factor for skin carcinogenesis. Although comprehensive and well designed, the agricultural epidemiological study was not sufficient to characterize the direct contribution of the insecticide and solar radiation in melanomagenesis. Several studies have explored the synergistic effect of certain chemicals with UV radiation, increasing its deleterious effects on the skin. We hypothesized that carbaryl exposure associated with UV solar radiation may induce melanocyte transformation. This study aimed to characterize human melanocytes after individual or combined exposure to carbaryl (100 μM) and solar radiation (375 mJ/cm2). In a microarray analysis, carbaryl, but not solar radiation, induced an important oxidative stress response, evidenced by the upregulation of antioxidant genes, such as Hemeoxygenase-1 (HMOX1), and downregulation of Microphtalmia-associated Transcription Factor (MITF), the main regulator of melanocytic activity; results were confirmed by qRT-PCR. Carbaryl and solar radiation induced a gene response suggestive of DNA damage and cell cycle alteration. The expression of genes in these categories was notably more intense in the combined treatment group, in a synergistic manner, for CDKN1A, BRCA1/2 and MDM2 genes. Likewise, flow cytometry assays demonstrated S-phase cell cycle arrest, reduced apoptosis levels and faster induction of cyclobutane pyrimidine dimers (CPD) lesions in carbaryl treated groups. Our data suggests that carbaryl is genotoxic to human melanocytes, especially when associated with solar radiation.
2017-03-15 | GSE79579 | GEO
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Project description:The response of microRNAs (miRNAs) to solar ultraviolet radiation (UVR) in human melanocytes while in their natural environment, and in particular, melanocytes from persons with a history of melanoma versus those from healthy persons, have yet to be described. Here, we used laser capture microdissection (LCM) to isolate and subsequently profile the expression of miRNAs in a pure population of melanocytes from human volunteers exposed to physiological doses of simulated sunlight (ssUVR). The majority of the UV-responsive miRNAs in the melanocytes of melanoma patients were down-regulated in expression when compared to those in the melanocytes of healthy individuals. De-repressed genes associated with these down-regulated UV-miRNAs belonged to regulatory modules involved in controlling the epithelial-to-mesenchymal transition (EMT), apoptosis, and immune-evasion, processes reputedly linked to melanoma.
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Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression. Two-condition experiment, Normoxic MSCs vs. Hypoxic MSCs.
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Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
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