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

Research output: Contribution to journalArticle

Standard

HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5. / Newie, Inga; Søkilde, Rolf; Persson, Helena; Jacomasso, Thiago; Gorbatenko, Andrej; Borg, Åke; De Hoon, Michiel; Pedersen, Stine F.; Rovira, Carlos.

In: Scientific Reports, Vol. 6, 35664, 18.10.2016.

Research output: Contribution to journalArticle

Harvard

APA

CBE

MLA

Vancouver

Author

RIS

TY - JOUR

T1 - HER2-encoded mir-4728 forms a receptor-independent circuit with miR-21-5p through the non-canonical poly(A) polymerase PAPD5

AU - Newie, Inga

AU - Søkilde, Rolf

AU - Persson, Helena

AU - Jacomasso, Thiago

AU - Gorbatenko, Andrej

AU - Borg, Åke

AU - De Hoon, Michiel

AU - Pedersen, Stine F.

AU - Rovira, Carlos

PY - 2016/10/18

Y1 - 2016/10/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84992027415&partnerID=8YFLogxK

U2 - 10.1038/srep35664

DO - 10.1038/srep35664

M3 - Article

VL - 6

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 35664

ER -