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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Bibliographic Details
Published in:Scientific reports Vol. 6; no. 1; p. 35664
Main Authors: Newie, Inga, Søkilde, Rolf, Persson, Helena, Jacomasso, Thiago, Gorbatenko, Andrej, Borg, Åke, de Hoon, Michiel, Pedersen, Stine F., Rovira, Carlos
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 18.10.2016
Nature Publishing Group
Subjects:
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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
Online Access:Get full text
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Summary: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.
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These authors contributed equally to this work.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep35664