Project description:We analysed the molecular effects on gene modulation exerted by inhibition of miRNA 503 expression in mesothelioma. In vitro results demonstrated that its inhibition determined apoptosis and reduced cancer properties in two different mesothelioma cell lines including one resistant to conventional chemotherapeutic treatment.
Project description:We analysed the molecular effects on gene modulation exerted by aglianico grape seed extract (AGS) in mesothelioma. Previous results allowed to demonstrate that AGS polar extracts determined apoptosis in three different mesothelioma cell lines including one resistant to conventional chemotherapeutic treatment. In addition this treatment affected tumorigenic and invasive properties of these cells We used microarrays to identify molecular pathway deregulated by AGS treatment and involved in apoptosis induction.
Project description:More than half of malignant mesothelioma patients show alterations in the BAP1 tumour suppressor gene. Being a member of the Polycomb repressive deubiquitinating (PR-DUB) complex, BAP1 loss results in an altered epigenome which may create new vulnerabilities that remain largely unknown. Here we performed a CRISPR/Cas9-kinome screen in mesothelioma cells that identified two kinases in the Mevalonate/Cholesterol biosynthesis pathway. Furthermore, our analysis of chromatin, expression and genetic perturbation data in mesothelioma cells suggests a dependency on Polycomb repressive complex 2 (PRC2) mediated silencing. Pharmacological inhibition of PRC2 elevates the expression of cholesterol biosynthesis genes only in BAP1-deficient mesothelioma, thereby sensitizing these cells to the combined targeting of PRC2 and the mevalonate pathway. Finally, by subjecting autochthonous Bap1-deficient mesothelioma mice or xenografts to mevalonate pathway inhibition (Zoledronic Acid) and PRC2 inhibition (Tazemetostat), we demonstrate a potent anti-tumour effect, suggesting a targeted combination therapy for Bap1-deficient mesothelioma
Project description:Desmoplastic malignant mesothelioma is a rare tumor. Due to the rarity, genomic profile of desmoplastic malignant mesothelioma is not unveiled. To elucidate genomic profile of desmoplastic malignant mesothelioma, we used illumina infinium omini exomeexpress in an established patient-derived cell line of desmoplastic malignant mesothelioma.
Project description:The transcriptomic responses of syndecan-1 silencing in a human mesothelioma cell line was followed with microarray analysis. To project the transcriptome analysis on the full-dimensional picture of cellular regulation, we applied a novel method of network enrichment analysis which elucidated signalling relations between differentially expressed genes and pathways acting via various molecular mechanisms. Our results suggest that syndecan-1 regulates cell proliferation in a highly complex way, although the exact contribution of the altered pathways necessitates further functional studies. Gene expression profiles (Human Gene 1.0 ST) of malignant mesothelioma cells were studied in cells silenced for syndecan-1 (N=3) and scrambled control cells (N=3)