Our data show that INPP4B modulates AR activity in normal prostate and its loss contributes to the AR-dependent transcriptional profile in prostate cancer.
INPP4B inhibits PtdIns(3,4)<i>P</i><sub>2</sub>-mediated AKT activation in breast and prostate cancer; however, INPP4B expression is increased in acute myeloid leukaemia (AML), melanoma and colon cancer where it paradoxically promotes cell proliferation, transformation and/or drug resistance.
Then, we explored the role of INPP4B in prostate cancer progression via transfection of a Flag-INPP4B plasmid into PC3 and DU145 cells in vitro and in vivo.
Enforced expression of microRNA-590-3p led to repression of inositol polyphosphate 4-phosphatase type II messenger RNA and protein expression, as well as upregulation of p-Akt, p-FoxO3a, and cyclin D1 and downregulation of p21 expression in prostate cancer cell lines.
Our results demonstrated that the combination of INPP4B gene transfection and PARP inhibitor had a synergistic antitumor effect on PC3 cells, which was expected to shed new light on combined biological therapy in castration therapy-resistant prostate cancer.