miR-503 Represses Human Cell Proliferation and Directly Targets the Oncogene DDHD2 by Non-Canonical Target Pairing
Abstract
The 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. Results: Here 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. Conclusions: Our 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.
Department
Subject
mirna
mirna targeting
proliferation
ago2 immunoprecipitation
rip-seq
mirna targets
mirna target pairing
mir-503
mirna
non-canonical pairing
negative feedback loop
enrichment analysis
tumor-suppressor
messenger-rnas
lung-cancer
micrornas
quiescence
binding
genes
identification
biotechnology & applied microbiology
genetics & heredity
mirna targeting
proliferation
ago2 immunoprecipitation
rip-seq
mirna targets
mirna target pairing
mir-503
mirna
non-canonical pairing
negative feedback loop
enrichment analysis
tumor-suppressor
messenger-rnas
lung-cancer
micrornas
quiescence
binding
genes
identification
biotechnology & applied microbiology
genetics & heredity
Collections
Related items
Showing items related by title, author, creator and subject.
-
Prediction and verification of microRNA targets by MovingTargets, a highly adaptable prediction method
Burgler, Craig; Macdonald, Paul M. (BMC Genomics, 2005-06-08)Background: MicroRNAs (miRNAs) mediate a form of translational regulation in animals. Hundreds of animal miRNAs have been identified, but only a few of their targets are known. Prediction of miRNA targets for translational ... -
Determination of how miRNAs mediate repression in Drosophila and the essential role of the oskar mRNA in egg chamber development
Reich, John Curtis (2009-12)miRNAs are important regulators of gene expression. These small RNAs function throughout development and regulate translation of a number mRNAs. miRNAs exert their affect on translation as part of the RNP complex RISC. ... -
Characterizing miRNA mediated regulation of proliferation
Polioudakis, Damon Constantine (2014-05)Cell proliferation is a fundamental biological process, and the ability of human cells to transition from a quiescent to proliferative state is essential for tissue homeostasis. Most cells in eukaryotic organisms are in a ...