Zhang Wei, Liu Zihao, Wen Simeng, Shao Yuan, Yang Zhen, Wang Yong
Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.
Department of Urology, Affiliated Hospital of Hebei University, Hebei, China.
Discov Oncol. 2025 May 30;16(1):967. doi: 10.1007/s12672-025-02625-w.
Prostate cancer (PCa) is one of the most common cancers worldwide. Nei endonuclease VIII-like 3 (NEIL3) plays important roles in diverse cancers. In this study, we found that NEIL3 was overexpressed in PCa tissues and cell lines. NEIL3 over-expression was associated with worse prognostic outcomes in PCa patients. In vitro, PCa cell proliferation, invasion, and migration could be significantly inhibited with knocking down NEIL3 by inactivating the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of the rapamycin (mTOR) signaling. Besides, we found that the expression of high-mobility gene group A2 and androgen receptor (AR) were upregulated in PCa tissues, and their expression was decreased in C4-2 cells treated with siNEIL3. Nevertheless, R1881 could enhance si-NEIL3-inhibited PI3K, AKT and mTOR phosphorylation levels in both C4-2 cells and PC-3M. In conclusion, NEIL3 could promote the progression of PCa by activating PI3K/AKT/mTOR signaling in PCa cells. Therefore, these results may provide a potential molecular target for PCa treatment.
前列腺癌（PCa）是全球最常见的癌症之一。内核酸酶VIII样3（NEIL3）在多种癌症中发挥重要作用。在本研究中，我们发现NEIL3在PCa组织和细胞系中过表达。NEIL3过表达与PCa患者较差的预后结果相关。在体外，通过使磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素哺乳动物靶蛋白（mTOR）信号失活来敲低NEIL3，可显著抑制PCa细胞的增殖、侵袭和迁移。此外，我们发现高迁移率族蛋白A2（HMGA2）和雄激素受体（AR）在PCa组织中的表达上调，而在用siNEIL3处理的C4-2细胞中它们的表达下降。然而，R1881可增强siNEIL3抑制的C4-2细胞和PC-3M细胞中PI3K、AKT和mTOR的磷酸化水平。总之，NEIL3可通过激活PCa细胞中的PI3K/AKT/mTOR信号促进PCa进展。因此，这些结果可能为PCa治疗提供一个潜在的分子靶点。
