Project description:miR-135b expression is higher in myxoid liposarcoma cell lines than in adipose-derived mesenchymal cell line, as well as in myxoid liposarcoma tumors than in adjacent normal prostate tissues.To further investigate the molecular mechanisms regulated by miR-135b, we performed mRNA microarray analysis of cell cultures from myxoid liposarcoma cell line after transfections with miR-135b mimic or negative control.
Project description:In order to identify new key molecules in the pathogenesis of myxoid liposarcoma, we performed comparative gene expression profiling in myxoid liposarcoma and fat tissue samples.
Project description:Myxoid liposarcoma (MLS) is the second most common type of liposarcoma and is characterized by the fusion oncogene FUS‐DDIT3 or the less common EWSR1‐DDIT3. While the presence of FUS-DDIT3 as a driver oncoprotein in most MLS cases has been confirmed, the exact molecular action behind the capacity of FUS-DDIT3 for transformation is still unclear and therefore creates a challenge in finding new treatments against this type of cancer. The importance of the microenvironment for tumor progression have long been accepted and might also influence the effect of the fusion oncoprotein. However, due to a lack of relevant experimental model systems, it has been challenging to examine the microenvironmental impact in myxoid liposarcoma development. Therefore, we have developed a new model system utilizing scaffolds derived from myxoid liposarcoma patient-derived xenograft tumors that are decellularized and then repopulated with sarcoma cell lines. This cell culture system mimics in vivo-like tumor cell growth conditions and induce transcriptional changes within the cells. In order to investigate the effect of the microenvironment as well as the fusion oncogene, we analyzed myxoid liposarcoma cell lines as well as fibrosarcoma cells with and without ectopic FUS-DDIT3 expression cultured in scaffolds and adherent two-dimensional growth conditions. We identified several gene networks and processes that are uniquely associated with FUS-DDIT3 expression and with the microenvironment, respectively. The development of patient-derived scaffolds opens up new possibilities to understand tumor development.
Project description:In order to identify new key molecules in the pathogenesis of myxoid liposarcoma, we performed comparative gene expression profiling in myxoid liposarcoma and fat tissue samples. Whole genome microarray analysis was performed on eight primary myxoid liposarcoma samples and an RNA pool of eight healthy fat tissue samples.
Project description:FUS-CHOP and EWS-CHOP balanced translocations characterize myxoid liposarcoma which encompasses myxoid (ML) and round cell (RC) variants initially believed to be distinct diseases. Currently, myxoid and RC liposarcoma are regarded to represent the well differentiated and the poorly differentiated ends, respectively, within spectrum of myxoid liposarcoma where the fusion proteins blocking lipogenic differentiation play a role in tumor initiation while molecular determinants associated to progression to RC remain poorly understood. Activation of AKT pathway sustained by PIK3CA and PTEN mutations and growth factor receptor signalling such as RET and IGF1R have been recently correlated with the increasing of aggressiveness and RC. Aim of the present study is to elucidate molecular events involved in driving round cell progression analyzing two small series of MLS selected to be representative of the two end of the gamut: the pure myxoid (0% of RC component) and RC with high cellular component (≥80%).
Project description:FUS-CHOP and EWS-CHOP balanced translocations characterize myxoid liposarcoma which encompasses myxoid (ML) and round cell (RC) variants initially believed to be distinct diseases. Currently, myxoid and RC liposarcoma are regarded to represent the well differentiated and the poorly differentiated ends, respectively, within spectrum of myxoid liposarcoma where the fusion proteins blocking lipogenic differentiation play a role in tumor initiation while molecular determinants associated to progression to RC remain poorly understood. Activation of AKT pathway sustained by PIK3CA and PTEN mutations and growth factor receptor signalling such as RET and IGF1R have been recently correlated with the increasing of aggressiveness and RC. Aim of the present study is to elucidate molecular events involved in driving round cell progression analyzing two small series of MLS selected to be representative of the two end of the gamut: the pure myxoid (0% of RC component) and RC with high cellular component (≥80%).
Project description:MicroRNAs (miRNAs, miRs) are small noncoding RNAs, which control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumor suppressor genes, play important roles in carcinogenesis. Myxoid liposarcomas (MLS) are characterized by t(12;16)(q13;p11) translocation and expression of TLS/CHOP chimeric transcripts (various types) which encode different oncogenic proteins. TLS-CHOP is important for the molecular mechanisms in the development of MLS, but the involvement in microRNA expression still remain poorly understood. Thus we explored the target microRNA of TLS-CHOP influence cell-proliferation or cell death with microarray. MicroRNAs (miRNAs, miRs) are small noncoding RNAs, which control or are controlled by the dysregulation of multiple protein-coding oncogenes or tumor suppressor genes, play important roles in carcinogenesis. Myxoid liposarcomas (MLS) are characterized by t(12;16)(q13;p11) translocation and expression of TLS/CHOP chimeric transcripts (various types) which encode different oncogenic proteins. TLS-CHOP is important for the molecular mechanisms in the development of MLS, but the involvement in microRNA expression still remain poorly understood. In this study, we have found that miR-486-5p (miR-486) expression level was downregulated by ectopic expression of TLS-CHOP fusion gene in mouse fibroblast cells (NIH3T3). In addition, we found overexpression of miR-486 inhibited the cell growth in the 2645/94 cells and in situ hybridization of miR-486 showed MLS tissues had lower signal intensity compared with non-tumor tissues. Thus we explored the target genes of miR-486 influence cell-proliferation or cell death with microarray. We compared the microRNA profiles of cells treated with TLS-CHOP or empty vector about NIH-3T3 cell-line. We compared the whole mRNA profiles of cells transfected with miR-486 oligonucleotides or control oligo about myxoid liposarcoma cell-line.