biostudies-literatureSilipo MMedical Research Council536-543https://www.ebi.ac.uk/biostudies/studies/S-EPMC5449083biostudies-literatureUnknown14(5)The human epidermal growth factor receptor 2 (HER2)/receptor tyrosine-protein kinasebB-2 (ERBB2) is overexpressed in 20-30% of breast tumors leading to faster growing and more aggressive tumors. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumor suppressor by effectively blocking HER2 activity and cell proliferation, while promoting apoptosis. In the present study we investigated HER2 pre-mRNA regulatory sequences and splicing factors which regulate the alternative splicing of Herstatin. A Herstatin minigene, comprising exon 8/intron 8/exon 9 of HER2 was generated and subsequent in vitro splicing assays revealed that RNA secondary structure and somatic mutations did not impact on inRNA biologyHow is Herstatin, a tumor suppressor splice variant of the oncogene HER2, regulated?PMC5449083MC_PC_14101Silipo MLennard TTyson-Capper AGautrey HSatam SfalseHow is Herstatin, a tumor suppressor splice variant of the oncogene HER2, regulated?The human epidermal growth factor receptor 2 (HER2)/receptor tyrosine-protein kinasebB-2 (ERBB2) is overexpressed in 20-30% of breast tumors leading to faster growing and more aggressive tumors. Alternative splicing generates a functionally distinct HER2 variant called Herstatin, which is produced by the inclusion of intron 8. Herstatin acts as a tumor suppressor by effectively blocking HER2 activity and cell proliferation, while promoting apoptosis. In the present study we investigated HER2 pre-mRNA regulatory sequences and splicing factors which regulate the alternative splicing of Herstatin. A Herstatin minigene, comprising exon 8/intron 8/exon 9 of HER2 was generated and subsequent in vitro splicing assays revealed that RNA secondary structure and somatic mutations did not impact on in2017-01-01T00:00:00Z2017 May2025-04-04T12:36:26.828Z2019-03-27T02:46:15ZS-EPMC54490832793542510.1080/15476286.2016.1267074