title: Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells.
abstract: The 4-phosphatase Inositol polyphosphate 4-phosphatase II (INPP4B) is a regulator of the PI3K signalling pathway and functions to suppress or promote activation of downstream kinases depending on cell type and context. Here we report the identification of a novel small transcript variant of INPP4B (INPP4B-S) that has a role in promoting proliferation of colon and breast cancer cells. INPP4B-S differed from full length INPP4B (INPP4B-FL) by the insertion of a small exon between exons 15 and 16 and the deletion of exons 20-24. Nevertheless, INPP4B-S retained all the functional domains of INPP4B-FL and was similarly located to the cytoplasm. Overexpression of INPP4B-S increased, whereas selective knockdown of INPP4B-S reduced the rate of proliferation in HCT116 and MCF-7 cells. These results warrant further investigation of the role INPP4B-S in activation of downstream kinases and in regulation of cancer pathogenesis.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Croft
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia.
authors.forename: Su Tang
authors.initials: ST
authors.lastname: Guo
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia.
authors.forename: Simonne
authors.initials: S
authors.lastname: Sherwin
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Farrelly
authors.affiliation: School of Medicine and Public Health, University of Newcastle, NSW 2308, Australia.
authors.forename: Xu Guang
authors.initials: XG
authors.lastname: Yan
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, NSW 2308, Australia. Electronic address: Xu.Zhang@newcastle.edu.au.
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Zhang
authors.affiliation: School of Medicine and Public Health, University of Newcastle, NSW 2308, Australia. Electronic address: ChenChen.Jiang@newcastle.edu.au.
authors.forename: Chen Chen
authors.initials: CC
authors.lastname: Jiang
mesh_terms: D017398:Alternative Splicing; D001483:Base Sequence; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D003106:Colon / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D020033:Protein Isoforms; D010744:Phosphoric Monoester Hydrolases; C053153:phosphatidylinositol-3,4-bisphosphate 4-phosphatase
keywords: Breast cancer; Colon cancer; INPP4B; Transcript variant