Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
Project description:Inflammatory conditions can contribute to tumor formation. However, any clear marker predicting progression to cancer are still lacking. The aim of our study was to analyze microRNA modulations accompanying inflammation-induced tumor development to determine whether these microRNA may jointly affect the expression of genes involved in cancer. For this purpose, we used the well-established azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model of colitis-associated cancer. We performed a microRNA microarray to establish microRNA expression profiles in mouse whole colon at early and late time points during inflammation and/or tumor growth. Chronic inflammation and carcinogenesis were associated with distinct changes in microRNA expression. Nevertheless, prediction algorithms of microRNA-mRNA interactions and computational analyses based on ranked microRNA lists consistently identified putative target genes that play essential roles in tumor growth or belong to key carcinogenesis-related networks or signaling pathways. Hence, inflammation, through microRNA, may affect unexpected genes or signaling pathways, thereby contributing to carcinogenesis. The present method can lead to the identification of novel genes or signaling pathways involved in cancer development.
Project description:Inflammatory conditions can contribute to tumor formation. However, any clear marker predicting progression to cancer are still lacking. The aim of our study was to analyze microRNA modulations accompanying inflammation-induced tumor development to determine whether these microRNA may jointly affect the expression of genes involved in cancer. For this purpose, we used the well-established azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model of colitis-associated cancer. We performed a microRNA microarray to establish microRNA expression profiles in mouse whole colon at early and late time points during inflammation and/or tumor growth. Chronic inflammation and carcinogenesis were associated with distinct changes in microRNA expression. Nevertheless, prediction algorithms of microRNA-mRNA interactions and computational analyses based on ranked microRNA lists consistently identified putative target genes that play essential roles in tumor growth or belong to key carcinogenesis-related networks or signaling pathways. Hence, inflammation, through microRNA, may affect unexpected genes or signaling pathways, thereby contributing to carcinogenesis. The present method can lead to the identification of novel genes or signaling pathways involved in cancer development. miRNA microarray profiling in whole mouse colon at 4 time points during AOM/DSS treatment. Controls : PBS, DSS alone or AOM alone, at two time points; 10 experimental conditions, 5 replicates per experimental conditions, one replicate per array hybridized in dual color with a commercial reference (Universal Reference, Miltenyi Biotec GmbH)
Project description:SPO11-promoted DNA double-strand breaks (DSBs) formation is a crucial step for meiotic recombination, and it is indispensable to detect the broken DNA ends accurately for dissecting the molecular mechanisms behind. Here, we report a novel technique, named DEtail-seq (DNA End tailing followed by sequencing), that can directly and quantitatively capture the meiotic DSB 3’ overhang hotspots at single-nucleotide resolution.