Gene Expression Regulation and Cancer
Start date: Oct 1, 2012,
End date: Sep 30, 2016
Cancer remains the most predominant cause of premature death in Europe. It constitutes a major public health problem with 1.28 million predicted deaths in the European Union in 2011. Changes in the gene expression patterns are a key feature of cancer cell transformation through an increase in expression of genes that promote carcinogenesis (oncogenes) and/or a decrease in expression of genes that prevent it (tumour suppressor genes). Chromatin-structure and microRNAs (miRNAs) both play important roles in this process and have been found to be critical in the development of human pathologies.DNA is packaged inside cells through a scaffold of proteins, constituting the chromatin. The chromatin not only has a structural role, but it also plays an active role in other processes including gene expression. The SWI/SNF complex is an ATP-dependent chromatin-remodelling complex that uses the energy from ATP hydrolysis to modify the interactions between DNA and histones. In this way, the SWI/SNF complex can render the DNA accessible or inaccessible to the transcription machinery. Ever increasing evidence demonstrates that some components of the SWI/SNF complex act as tumour suppressors and their dysregulation is involved in human cancer development.MiRNAs are a recently discovered class of small RNA molecules that regulate gene expression at the post-transcriptional level. Due to their small size and unusual nature, miRNAs were not discovered in humans until 2000. Today, over one thousand miRNAs have been identified in the human genome. Aberrant biogenesis and/or expression of miRNAs has been linked to human diseases including cancer.Pioneering reports suggest a functional relationship between the SWI/SNF complex and miRNAs. MiRNAs regulate the expression of chromatin remodelling complex proteins, which in turn have been shown to influence levels of miRNA transcription. In the present proposal, I will study this regulatory relationship in the context of cancer.
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