Recent evidence indicates that miRNAs can influence tumorigenesis and function as either tumour suppressors or oncogenes. Consequently, differential expression of specific miRNAs in various tumours might become a powerful tool to aid in the diagnosis and treatment of cancer. Moroever, delivery of miRNAs or “antagomirs” that antagonize miRNA function may be an attractive new cancer-treament modality. Continued research into miRNA function is therefore warranted that might lead to an advanced understanding of the mechanisms that lead to tumorigenesis. To validate miRNA for diagnostic and therapeutic purposes, it is crucial to (i) establish a causal relationship between differential miRNA expression and the cancerous phenotype and (ii) to better understand the physiologic consequences of modulating miRNAs expression, particularly since many of the targets of most miRNAs remain to be discovered. Hence, establishing a causal relationship between a given miRNA and malignancy following hepatic over/under-expression of this miRNA should allow us to exclude fortuitous associations between miRNA expression levels and the cancerous phenotype and hereby strenghten its intrinsic diagnostic and therapeutic relevance. We will also investigate the interactions between epigenetic control of gene expression and miRNA regulation. This project aims at addressing some of these outstanding questions in miRNA biology and cancer using hepatocellular carcinoma (HCC) as a model, given its poor prognosis and high prevalence. However, the available technology is amenable to other cancer types.

 

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