miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing |
| |
Authors: | Damon Polioudakis Nathan S Abell Vishwanath R Iyer |
| |
Affiliation: | Department of Molecular Biosciences, Center for Systems and Synthetic Biology, Institute for Cellular and Molecular Biology, University of Texas, Austin, Texas USA |
| |
Abstract: | BackgroundThe pathways regulating the transition of mammalian cells from quiescence to proliferation are mediated by multiple miRNAs. Despite significant improvements in our understanding of miRNA targeting, the majority of miRNA regulatory networks are still largely unknown and require experimental validation.ResultsHere we identified miR-503, miR-103, and miR-494 as negative regulators of proliferation in primary human cells. We experimentally determined their genome wide target profiles using RNA-induced silencing complex (RISC) immunoprecipitations and gene expression profiling. Analysis of the genome wide target profiles revealed evidence of extensive regulation of gene expression through non-canonical target pairing by miR-503. We identified the proto-oncogene DDHD2 as a target of miR-503 that requires pairing outside of the canonical 5′ seed region of miR-503, representing a novel mode of miRNA-target pairing. Further bioinformatics analysis implicated miR-503 and DDHD2 in breast cancer tumorigenesis.ConclusionsOur results provide an extensive genome wide set of targets for miR-503, miR-103, and miR-494, and suggest that miR-503 may act as a tumor suppressor in breast cancer by its direct non-canonical targeting of DDHD2.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1279-9) contains supplementary material, which is available to authorized users. |
| |
Keywords: | miRNA miRNA targeting Proliferation Ago2 immunoprecipitation RIP-seq miRNA targets miRNA target pairing miR-503 miRNA non-canonical pairing |
|
|