Development of novel therapy against human liposarcoma using siRNAlibrary

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The discovery of RNA interference (RNAi) in eukaryotic cells is a major breakthrough in the recent progress of the molecular and cellular biology. RNAi machineries exert biological functions in gene regulation, genome defense, chromatin architecture and dynamics. Today, RNAi has had an enormous impact on the development of novel disease models in animals. In addition, small interfering RNAs (siRNAs), the trigger molecules for RNA silencing, are likely to become invaluable tools for the treatment of various diseases.All of known human myxoid and round cell liposarcomas (MLS/RCLS) are associated with chromosomal translocations. These chromosomal translocations lead to gene fusions that encode chimeric oncoproteins consisting of an N terminus contributed by one of two related genes, TLS (also known as FUS) or EWS, and a C terminus contributed by the CHOP (also called GADD153) gene.In this project, we tried to identify the genes that implicated with tumorigenesis of MLS/RCLS using Lentiviral siRNA library. We infected human myxoid liposarcoma cell lines with Lentiviral siRNA library and we cloned some genes.On the other hand, MicroRNAs (miRNAs) are a family of 21. to 25-nucleotide, noncoding small RNAs that primarily function as gene regulators. MicroRNAs (miRNAs) have been suggested to play important roles in cell proliferation, apoptosis, and differentiation. And aberrant miRNA expression has been described for several human malignancies and tumour suppressor functions have been ascribed to this new class of small regulatory RNAs. Despite this knowledge, there is a lack of information regarding miRNA in the MLS/RCLS. In this project, we have tried to identify downstream miRNA of TLS-CHOP using microarray. And we identified some miRNAthat regulated TLS-CHOP. Interestingly, we transfected some of miRNA that regulated by TLS-CHOP, suppressed tumor growth MLS/RCLS cell lines. These data suggested that some miRNA become drugable target for MLS/RCS.