Functional identification of a novel transcript variant of INPP4B in human colon and breast cancer cells

Biochem Biophys Res Commun. 2017 Mar 25;485(1):47-53. doi: 10.1016/j.bbrc.2017.02.012. Epub 2017 Feb 8.

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.

Keywords: Breast cancer; Colon cancer; INPP4B; Transcript variant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Base Sequence
  • Breast / metabolism
  • Breast / pathology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Proliferation
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology
  • Exons
  • Female
  • HCT116 Cells
  • Humans
  • MCF-7 Cells
  • Phosphoric Monoester Hydrolases / analysis
  • Phosphoric Monoester Hydrolases / genetics*
  • Protein Isoforms / genetics
  • Transcription, Genetic

Substances

  • Protein Isoforms
  • Phosphoric Monoester Hydrolases
  • phosphatidylinositol-3,4-bisphosphate 4-phosphatase