Biochemical Identification and Functional Characterization of Microrna-Target Interactions In Growth Control And Cancer Transformation

Abstract

I used immunopurification coupled to microarray technology to identify a pool of potential miRNA targets in Drosophila S2 cells. Computational analysis suggested the existence of two distinct sets of microRNA targets that exhibit substantial differences in molecular and structural properties. My study further revealed a genome-wide correlation between binding site accessibility and target 3?UTR length, suggesting an unprecedented complexity of miRNA-target interactions. One target we identified is Socs36E, which contains a binding site for the growth regulatory microRNA, bantam. Genetic and functional analysis indicated Socs36E is a negative growth regulator and contributes to bantam?s loss-of-function phenotype. Socs36E acts as a potent oncogenic cooperating factor under elevated EGFR activity in a Drosophila tumor transformation model. Using an in vitro human cancer transformation model, I further demonstrated the human orthologs of Socs36E, the SOCS protein family members are potential cooperating factors of RasV12/EGF-driven cancer transformation in primary human cells.