Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China.
Breast Cancer Res Treat. 2023 Apr;198(3):437-446. doi: 10.1007/s10549-023-06876-5. Epub 2023 Feb 17.
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.
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.
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.
Our results provide evidence that high expression of POU3F2 promotes radioresistance in triple-negative breast cancer via Akt pathway activation by interacting with ARNT2.
POU3F2 与癌症的恶性行为和不良预后相关。然而，POU3F2 在乳腺癌中的功能和机制仍有待阐明。我们的研究旨在探讨 POU3F2 在三阴性乳腺癌和放疗中的作用。
通过 RT-PCR 和 Western blot 检测 POU3F2 的表达。MTT 法检测癌细胞的增殖。Transwell 检测和划痕愈合实验检测癌细胞的迁移。通过 Co-IP 确定与 POU3F2 相互作用的蛋白。基于在线数据库 GEPIA 进行生存分析。彗星实验检测辐射后 DNA 损伤。克隆形成实验评估放射敏感性。用 MDA-MB-231 乳腺癌细胞在 BALB/c 裸鼠中建立肿瘤异种移植模型，以体内研究 POU3F2 的作用。
我们发现 POU3F2 在乳腺癌细胞中表达显著上调，尤其是在三阴性乳腺癌中，且高表达 POU3F2 与乳腺癌患者的不良预后相关。功能分析显示，POU3F2 促进三阴性乳腺癌（TNBC）细胞的体外和体内增殖、迁移和侵袭。此外，POU3F2 的敲低降低了 TNBC 细胞的体外放射抵抗性。此外，POU3F2 通过与 ARNT2 相互作用，增强 Akt 通路的激活，从而促进 TNBC 细胞的增殖和放射抵抗性。
我们的研究结果表明，高表达的 POU3F2 通过与 ARNT2 相互作用激活 Akt 通路，促进三阴性乳腺癌的放射抵抗性。
