HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5

We previously reported that the human HER2 gene encodes the intronic microRNA mir-4728, which is overexpressed together with its oncogenic host gene and may act independently of the HER2 receptor. More recently, we also reported that the oncogenic miR-21-5p is regulated by 3′ tailing and trimming by...

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Vydáno v:	Scientific reports Ročník 6; číslo 1; s. 35664
Hlavní autoři:	Newie, Inga, Søkilde, Rolf, Persson, Helena, Jacomasso, Thiago, Gorbatenko, Andrej, Borg, Åke, de Hoon, Michiel, Pedersen, Stine F., Rovira, Carlos
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 18.10.2016 Nature Publishing Group
Témata:	13 38/61 692/4028/67/395 692/53 Apoptosis Basic Medicine Breast cancer Breast Neoplasms - genetics Cancer and Oncology Cancer och onkologi Carcinogenesis Cell and Molecular Biology Cell cycle Cell growth Cell Line, Tumor Cell- och molekylärbiologi Clinical Medicine ErbB-2 protein Female Gene expression Gene Expression Regulation, Neoplastic Humanities and Social Sciences Humans Kinases Klinisk medicin Medical and Health Sciences Medical research Medicin och hälsovetenskap Medicinska och farmaceutiska grundvetenskaper MicroRNAs MicroRNAs - genetics miRNA multidisciplinary Polyadenine Polynucleotide adenylyltransferase Proteins Receptor, ErbB-2 - genetics Ribonuclease RNA Nucleotidyltransferases - metabolism Science Signal Transduction Transcription Tumors Up-Regulation
ISSN:	2045-2322, 2045-2322
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Shrnutí:	We previously reported that the human HER2 gene encodes the intronic microRNA mir-4728, which is overexpressed together with its oncogenic host gene and may act independently of the HER2 receptor. More recently, we also reported that the oncogenic miR-21-5p is regulated by 3′ tailing and trimming by the non-canonical poly(A) polymerase PAPD5 and the ribonuclease PARN. Here we demonstrate a dual function for the HER2 locus in upregulation of miR-21-5p; while HER2 signalling activates transcription of mir-21, miR-4728-3p specifically stabilises miR-21-5p through inhibition of PAPD5. Our results establish a new and unexpected oncogenic role for the HER2 locus that is not currently being targeted by any anti-HER2 therapy.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 These authors contributed equally to this work.
ISSN:	2045-2322 2045-2322
DOI:	10.1038/srep35664