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

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

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.

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Abbreviations

TNBC:

Triple-negative breast cancer

ER:

Estrogen receptor

PR:

Progesterone receptor

HER:

Human epidermal growth factor receptor 2

RT:

Radiotherapy

ICI:

Immune checkpoint inhibitors

TBP:

TATA-binding protein

SCLC:

Small cell lung cancer

NSCLC:

Non-small cell lung cancer

ARNT2:

Aryl hydrocarbon receptor nuclear translocator 2

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Funding

This work was supported by the Natural Science Foundation of Guangdong (Grant No. 2021A1515011537).

Author information

Author notes

  1. Han Zhang, Jieling Zheng and Yiming Fu have contributed equally to this article.

Authors and Affiliations

  1. Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Han Zhang, Yiming Fu, Jing Ling, ZiShen Liu, Xiaotong Lin, Xin Dong, Tingting Tan, Zhaoze Guo & Guozhu Xie

  2. The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China

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

  3. Department of Radiology, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Jieling Zheng

  4. Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China

    Zhaoze Guo

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  1. Han Zhang
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Contributions

GX and ZG contributed to the study conception and design. Material preparation, data collection, and analysis were performed by HZ, JZ, YF, and JL, ZL, XL, XD, YS, TT. The first draft of the manuscript was written by HZ and all authors commented on previous versions of the manuscript. All authors approved the final manuscript for publication.

Corresponding authors

Correspondence to Zhaoze Guo or Guozhu Xie.

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Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All animal experiments were approved by the Institutional Animal Care and Use Committee of Nanfang Hospital and obeyed the rules required by the Guide for the Care and Use of Laboratory Animals. Registration No. of the study: NFYY-2021-0831 (The review list of the animal ethic committee to the animal protocol has been uploaded).

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Zhang, H., Zheng, J., Fu, Y. et al. Overexpression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation. Breast Cancer Res Treat 198, 437–446 (2023). https://doi.org/10.1007/s10549-023-06876-5

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