Reverse engineering microRNA-related regulatory networks
作者单位：Center for Computational Biology and Bioinformatics Columbia Initiative in Systems BiologyColumbia University
会议名称：《第五届全国生物信息学与系统生物学学术大会暨国际生物信息学前沿研讨会高通量时代的生物信息学与系统生物学》
会议日期：2012年
学科分类：0710[理学-生物学] 07[理学] 071007[理学-遗传学]
关 键 词：microRNA activity biogenesis sponge regulation post-transcriptional
摘 要：Background:microRNAs(miRs) have emerged as key regulators of both normal and pathologic phenotypes,including *** activities and biogenesis of miRs are heavily *** of physiologic miR activity and biogenesis has been shown to play an important role in tumor initiation and ***,few modulators of miR activity and biogenesis have been characterized,and both the extent and relevance of their role in controlling normal cell physiology and pathogenesis are poorly understood. Methods:Systematic approaches were exploited to dissect microRNA-related post- transcriptional regulatory networks that are associated with human ***,by analyzing mRNA and miR expression profiles of a large set of glioblastoma patient samples, miR activity and biogenesis regulations have been studied in a genome-wide scale. Results:First,genome-wide screening of miR activity regulators uncovered a previously-uncharacterized layer of post-transcriptional regulation,involving 7,000 RNAs that act as miR sponges and participate in more than 248,000 miR program-mediated (mPM) *** regulation layer also includes 148 genes that regulate individual miR activity on its targets through alternative,nonsponge *** mPM interactions as a network mediate crosstalk between canonical oncogenic pathways and connect genetically distant genes,which was experimentally validated in tumor cell *** mPM interactions also provide mechanistic rationales for regulation of key genes in cancer,and largely explain missing genetic variations in various patient *** interaction networks were also reconstructed for breast,prostate,and ovarian ***,hundreds of novel regulators of miR biogenesis were discovered through a genome-wide screening using the same dataset as above.A subset of these regulators have been experimentally validated via high-,mid-,and low-throughput profiling of primary,precursor,and mature miRs in additio