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    Histone citrullination represses miRNA expression resulting in increased oncogene mRNAs in somatolactotrope cells.

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    Authors
    DeVore, Stanley B
    Young, Coleman H.
    Li, Guangyuan
    Sundararajan, Anitha
    Ramaraj, Thiruvarangan
    Mudge, Joann
    Schilkey, Faye
    Muth, Aaron
    Thompson, Paul R
    Cherrington, Brian D.
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Pharmacology
    Thompson Lab
    Document Type
    Journal Article
    Publication Date
    2018-09-14
    Keywords
    Animals
    Antibodies, Monoclonal
    Bacterial Toxins
    Enterotoxins
    Enzyme-Linked Immunosorbent Assay
    Escherichia coli Proteins
    Immunoenzyme Techniques
    Mice
    citrullination
    epigenetics
    prolactinoma
    miRNA
    oncogenes
    Biochemistry
    Cell Biology
    Enzymes and Coenzymes
    Medicinal-Pharmaceutical Chemistry
    Molecular Biology
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    Link to Full Text
    https://mcb.asm.org/content/38/19/e00084-18.long
    Abstract
    Peptidylarginine deiminase (PAD) enzymes convert histone arginine residues into citrulline to modulate chromatin organization and gene expression. Although PADs are expressed in anterior pituitary gland cells, their functional role and expression in pituitary adenomas is unknown. To begin to address these questions, we first examined normal human pituitaries and pituitary adenomas and found that PAD2, PAD4 and citrullinated histones are highest in prolactinomas and somatoprolactinomas. In the somatoprolactinoma-derived GH3 cell line, PADs citrullinate histone H3, which is attenuated by a pan-PAD inhibitor. RNA-sequencing and ChIP studies show that the expression of microRNAs let-7c-2, miR-23b and miR-29c is suppressed by histone citrullination. Our studies demonstrate that these miRNAs directly target the mRNA of the oncogenes HMGA, IGF-1 and N-MYC, which are highly implicated in human prolactinoma/somatoprolactinoma pathogenesis. Our results are the first to define a direct role for PAD catalyzed histone citrullination in miRNA expression, which may underlie the etiology of prolactinoma and somatoprolactinoma tumors through regulation of oncogene expression.
    Source

    DeVore SB, Young CH, Li G, Sundararajan A, Ramaraj T, Mudge J, Schilkey F, Muth A, Thompson PR, Cherrington BD. 2018. Histone citrullination represses microRNA expression, resulting in increased oncogene mRNAs in somatolactotrope cells. Mol Cell Biol 38:e00084-18. Link to article on publisher's site

    DOI
    10.1128/MCB.00084-18
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/46401
    PubMed ID
    29987187
    Related Resources

    Link to article in PubMed

    Rights
    Copyright © 2018, American Society for Microbiology. Publisher PDF posted after 6 months as allowed by the publisher's author rights policy at https://journals.asm.org/content/statement-author-rights.
    ae974a485f413a2113503eed53cd6c53
    10.1128/MCB.00084-18
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    UMass Chan Faculty and Researcher Publications
    Thompson Lab Publications

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