Overexpression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation

Abstract

Abstract Purpose: POU3F2 is associated with malignant behaviors and poor prognosis in cancer. However, the function and mechanism of POU3F2 in breast cancer remains to be elucidated. The purpose of our study was to explore the role of POU3F2 in triple-negative breast cancer and radiotherapy. Methods:POU3F2 expression was examined by RT-PCR and Western Blot.Proliferation of cancer cells was measured by MTT assay.Migration of cancer cells was determined by Transwell assay and wound healing assay.To determine which proteins interact with POU3F2,co-IP was preformed.Survival analysis was performed by online database resources GEPIA and The Kaplan–Meier plotter.DNA damage after radiation was examined by Comet Assay.Radiosensetivity was evaluated with Clonogenic survival assays.Tumor xenograft was established with MDA-BA-231 breast cancer cells in BALB/c nude mice to explore the effect of POU3F2 in vivo. Results:We found that the expression of POU3F2 was significantly elevated in breast cancer cells, and higher POU3F2 expression was related to poor prognosis of patients with breast cancer. Functional assays revealed that POU3F2 promoted proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells in vitro and in vivo. In addition, knock-down of POU3F2 decreased the radioresistance of TNBC cells in vitro. Furthermore, POU3F2 could enhance the activation of the Akt pathway by interacting with ARNT2, thereby promoting proliferation and radioresistance in TNBC cells. Conclusions:Our results provide the first evidence that high expression of POU3F2 promotes radioresistance in triple negative breast cancer via Akt pathway activation by interacting with ARNT2.