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Role of DNA methylation in the regulation of lincRNAs in Hematological Malignancies (LincMHeM)
Date du début: 1 sept. 2013, Date de fin: 31 août 2016 PROJET  TERMINÉ 

"Traditionally, cancer researchers have focused their best efforts on studying the genetic alterations affecting the coding genes. Subsequently, it was observed that in addition to genetic alterations, epigenetic alterations affecting coding genes play an important role in tumor development. In the last decade, largely due to the ability to sequence the human genome and the observation that much of the genome is transcribed but not translated, genes known as ""non-coding RNAs"" (ncRNAs) have attracted great interest in relation to their biological functions and their role in human tumors. In addition to the small ncRNAs like miRNAs, is also revealing that the human genome also encodes numerous long non-coding RNAs (lncRNAs). Some of these lncRNAs are being found in the intergenic regions of the genome (long intergenic non-coding RNAs - lincRNAs). It is estimated that there may be more than 8000 lincRNAs in the human genome. The mechanism that regulates these lincRNAs and the functional mechanism of the vast majority of these lincRNAs are not known, but the few that have been studied are known to exert their function in the nucleus and to be involved in chromatin remodeling and transcription regulation. The expression of lincRNAs is altered in cancer, playing an important role in the initiation, prognosis and progression of human neoplasies. In this regard, preliminary results from our group show that DNA methylation may play an important role in the regulation of lincRNAs and probably in the pathogenesis of hematological malignancies.For all these reasons, the objectives of this “LincMHeM” proposal are to determine whether inappropriate DNA methylation is involved in regulating lincRNA expression, and if such deregulated lincRNAs are involved in pathogenesis and are potential therapeutic targets for treating B cell hematological malignancies (multiple myeloma, lymphoma and acute lymphoblastic leukemia)."