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    miR-503 Represses Human Cell Proliferation and Directly Targets the Oncogene DDHD2 by Non-Canonical Target Pairing

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    2015_02_Polioudakis.pdf (1.230Mb)
    Date
    2015-02
    Author
    Polioudakis, Damon
    Abell, Nathan S.
    Iyer, Vishwanath R.
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    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
    Cellular and Molecular Biology
    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
    URI
    http://hdl.handle.net/2152/43349
    Citation
    Polioudakis, Damon, Nathan S. Abell, and Vishwanath R. Iyer. "miR-503 represses human cell proliferation and directly targets the oncogene DDHD2 by non-canonical target pairing." BMC genomics, Vol. 16, No. 1 (Feb., 2015): 1.
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