学术报告
题目：Reverse Engineering microRNA-Related Regulatory Networks in Cancer
报告人：Xuerui Yang, Ph.D.
Center for Computational Biology & Bioinformatics, Herbert Irving Comprehensive Cancer Center, Columbia University
时间：Wednesday 10:30 a.m., February 15
地点：生命科学学院411会议室
Systematic approaches were exploited to dissect microRNA-related post-transcriptional regulatory networks that are associated with human cancers. Specifically, by analyzing mRNA and microRNA (miR) expression profiles of a large set of glioblastoma patient samples, miR activity and biogenesis regulations have been studied in a genome-wide scale. 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) interactions. This regulation layer also includes 148 genes that regulate individual miR activity on its targets through alternative, nonsponge mechanisms. These mPM interactions as a network mediate crosstalk between canonical oncogenic pathways and connect genetically distant genes, which was experimentally validated in tumor cell lines. The mPM interactions also provide a mechanistic rationale for down-regulation of PTEN in a large number of PTEN-intactpatients. 13 miR-mediatedPTENregulators, whose locus deletions are predictive ofPTENexpression variability in PTEN-intactpatients, were shown to modulate PTEN expression as well as cell growth rate in tumor cell lines.
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