Histone citrullination represses miRNA expression resulting in increased oncogene mRNAs in somatolactotrope cells.
Authors
DeVore, Stanley BYoung, Coleman H.
Li, Guangyuan
Sundararajan, Anitha
Ramaraj, Thiruvarangan
Mudge, Joann
Schilkey, Faye
Muth, Aaron
Thompson, Paul R
Cherrington, Brian D.
Document Type
Journal ArticlePublication Date
2018-09-14Keywords
AnimalsAntibodies, 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
Metadata
Show full item recordAbstract
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.00084-18Permanent Link to this Item
http://hdl.handle.net/20.500.14038/46401PubMed ID
29987187Related Resources
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