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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2023

17-02-2023 | Breast Cancer | Preclinical study

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

Authors: Han Zhang, Jieling Zheng, Yiming Fu, Jing Ling, ZiShen Liu, Xiaotong Lin, Xin Dong, Yao Sun, Tingting Tan, Zhaoze Guo, Guozhu Xie

Published in: Breast Cancer Research and Treatment | Issue 3/2023

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Abstract

Purpose

POU3F2 is associated with malignant behaviors and poor prognosis in cancer. However, the function and mechanism of POU3F2 in breast cancer remain to be elucidated. Our study aimed to explore the role of POU3F2 in triple-negative breast cancer and radiotherapy.

Methods

POU3F2 expression was examined by RT-PCR and Western blot. The 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 protein interacts with POU3F2, Co-IP was performed. Survival analysis was performed based on the online database GEPIA. DNA damage after radiation was examined by Comet Assay. Radiosensitivity was evaluated with clonogenic survival assays. A tumor xenograft model was established with MDA-MB-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, especially in TNBC, 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, the knockdown 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 evidence that high expression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation by interacting with ARNT2.
Appendix
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Metadata
Title
Overexpression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation
Authors
Han Zhang
Jieling Zheng
Yiming Fu
Jing Ling
ZiShen Liu
Xiaotong Lin
Xin Dong
Yao Sun
Tingting Tan
Zhaoze Guo
Guozhu Xie
Publication date
17-02-2023
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2023
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-023-06876-5

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