Abstract A5: microRNA response to hypoxic stress in soft tissue sarcoma cells

Many solid tumors encounter hypoxia; a state in which the tumor tissue is deprived of oxygen. Hypoxia is of great clinical importance since it promotes malignant progression by increasing genetic instability, angiogenesis, local invasion and distant metastases. Furthermore hypoxia may lower the susceptibility to apoptosis, and induce chemo/radiation therapy resistance. These alterations are in part mediated by hypoxia inducible transcription factors like HIF1 that affect gene expression. Less well studied in hypoxia is the relatively new level of post-transcriptional regulation by microRNAs. MiRNAs are small non-protein coding RNA molecules that regulate gene expression by binding to the 3′UTRs of target mRNAs, thereby causing translation inhibition and/or mRNA degradation. Several studies have identified hypoxia-regulated miRNAs (HRMs). However, the lack of a general HRM profile suggests cell type specific miRNA responses to hypoxic stress. In a pilot study with three cancer cell lines of different histogenetic origin we observed, in line with the current literature, strong hypoxic miRNA-responses in each cell line, but little overlap in HRMs among the cell lines. Therefore we decided to focus on the modulation of the hypoxic response by miRNAs in a single class of rare mesenchymal tumors, soft tissue sarcomas.

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