2013.12.9 -- 洪帅 长链非编码RNA和癌症的遗传学.pptVIP

Long noncoding RNAs and the genetics of cancer hongshuai Background? Regulatory roles of LncRNA in cancer Genetic association of lncRNA and cancer Diagnostics and therapeutic potential of lncRNAs in cancer Background? The majority of cancers arise via somatic mutations. The genetic component of cancer susceptibility has not yet been linked to individual genes The ENCODE project concluded that the non-protein-coding regions of the genome serve not only as a substrate for DNA-binding proteins that in turn govern both the expression and 3D architecture of the genome, but also as a template for the transcription of vast numbers of noncoding RNAs , which exhibit exquisite cell-specific and developmental dynamic expression patterns , capable of transacting a wide repertoire of regulatory functions (Amaral et al , 2008; Mercer et al , 2009). These noncoding RNAs can be grouped into two major classes: small noncoding RNAs (200 bp) and LncRNAs ( 200 bp, up to ~100 kb). they are frequently transcribed by RNA polymerase IIand can show complex splicing patterns. LncRNAs are found in sense or antisense orientation to protein-coding genes, within introns of protein-coding genes or in intergenic regions of the genome. lncRNAs function in cis or trans,Although the functions of only a minority have been described, their dynamic and regulated expression suggests that many more may be functional. LncRNAs can operate through a variety of mechanisms, their importance in many aspects of cell differentiationand homeostasis is well established. Regulatory roles of LncRNA in cancer LncRNAs can act through a number of mechanisms to control cancer state. Despite growing knowledge about the molecular mechanisms of lncRNA functions in cancer, the modesof action of most lncRNAs remain unclear. A broader under-standing of the mechanisms of action of lncRNAs, and the regulatory pathways, hierarchies and networks in wh