Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, 1 WenYuan Road, Nanjing, 210023, China.
Suzhou Key Laboratory of Medical Biotechnology, Suzhou Vocational Health College, Suzhou, China.
Med Oncol. 2023 Jul 15;40(8):242. doi: 10.1007/s12032-023-02110-w.
Prostate cancer (PCa) refers to epithelial malignancies occurring in prostate and is the most commonly diagnosed cancer among men. Flap structure-specific endonuclease 1 (FEN1) is one of the major base excise repair enzymes and is abnormally expressed in a variety of cancers, which contributes to cancer progression. Targeting FEN1 serves as a potent strategy for cancer therapy. However, how FEN1 acts on PCa cell proliferation and its role in chemotherapeutic response remain largely unknown. In this study, we show that knockdown of FEN1 by CRISPR/Cas9 system impedes the proliferation and migration of PCa cells. FEN1 Inhibitor SC13 induced DNA damage accumulation and further resulted in apoptosis of PCa cells. Furthermore, genetic knockdown of FEN1 or inhibition of FEN1 by SC13 promoted DNA damage and enhanced docetaxel (DTX)-induced chemotherapeutic response in PCa cells. Collectively, these findings demonstrate the importance of FEN1 in PCa cell proliferation and implicate FEN1 as a promising target for monotherapy or combination therapeutic strategy in PCa treatment.
前列腺癌（PCa）是指发生于前列腺的上皮性恶性肿瘤，是男性最常见的癌症之一。 flap structure-specific endonuclease 1（FEN1）是主要的碱基切除修复酶之一，在多种癌症中异常表达，促进癌症进展。针对 FEN1 是癌症治疗的有效策略。然而，FEN1 如何影响 PCa 细胞增殖及其在化疗反应中的作用在很大程度上仍不清楚。本研究表明，CRISPR/Cas9 系统敲低 FEN1 可抑制 PCa 细胞的增殖和迁移。FEN1 抑制剂 SC13 诱导 DNA 损伤积累，进而导致 PCa 细胞凋亡。此外，FEN1 的基因敲低或 SC13 抑制 FEN1 可促进 DNA 损伤，并增强多西紫杉醇（DTX）诱导的 PCa 细胞化疗反应。综上所述，这些发现表明 FEN1 在 PCa 细胞增殖中的重要性，并暗示 FEN1 可能成为 PCa 治疗中单药或联合治疗策略的有前途的靶点。
