目前，非小细胞肺癌 (NSCLC) 仍然是导致癌症相关死亡的主要原因之一。化疗仍然是 NSCLC 的标准治疗方法。然而，耐药性的出现是肺癌治疗的主要障碍之一。植物同源结构域手指蛋白23 (PHF23) 在多个细胞命运中起着关键作用。然而，PHF23 在 NSCLC 中的临床意义和生物学功能仍然不清楚。我们采用癌症基因组图谱的数据挖掘，NCBI/GEO 数据挖掘以及西方印迹分析来表征 PHF23 在 NSCLC 细胞系和组织中的表达。采用免疫组化的统计分析和Kaplan-Meier Plotter数据库来研究 PHF23 的临床意义。我们进行了一系列的体内和体外实验，包括形成集落实验、细胞存活性实验、5-乙炔基-2'-脱氧尿苷 (EDU incorporation) 和 Transwell 迁移实验、流式细胞术、RT-PCR、基因集富集分析、共免疫沉淀分析和异种移植瘤模型，以证明 PHF23 对 NSCLC 细胞的化疗敏感性产生的影响，并阐明其潜在的分子机制。PHF23 在 NSCLC 细胞系和组织中过表达。高水平的 PHF23 与 NSCLC 患者的短期生存时间和对化疗的差异反应相关。PHF23 的过表达促进了细胞增殖、迁移，并通过促进 DNA 损伤修复使 NSCLC 细胞对顺铂和多西他赛敏感。作为下游调节因子，α-肌动蛋白-4 (ACTN4) 与 PHF23 的 PHD 结构域相互作用。此外，PHF23 通过抑制 ACTN4 的泛素化水平参与其稳定化。这些结果表明，PHF23 在 NSCLC 的发展和进展中起着重要作用，并暗示 PHF23 可能是 NSCLC 患者的治疗靶点。© 2023. 作者。

At present, non-small cell lung cancer (NSCLC) is still one of the leading causes of cancer-related deaths. Chemotherapy remains the standard treatment for NSCLC. However, the emergence of chemoresistance is one of the major obstacles to lung cancer treatment. Plant homologous structural domain finger protein 23 (PHF23) plays crucial roles in multiple cell fates. However, the clinical significance and biological role of PHF23 in NSCLC remain elusive. The Cancer Genome Atlas data mining, NCBI/GEO data mining, and western blotting analysis were employed to characterize the expression of PHF23 in NSCLC cell lines and tissues. Statistical analysis of immunohistochemistry and the Kaplan-Meier Plotter database were used to investigate the clinical significance of PHF23. A series of in vivo and in vitro assays, including assays for colony formation, cell viability, 5-ethynyl-2'-deoxyuridine (EDU incorporation) and Transwell migration, flow cytometry, RT-PCR, gene set enrichment analysis, co-immunoprecipitation analysis, and a xenograft tumor model, were performed to demonstrate the effects of PHF23 on the chemosensitivity of NSCLC cells and to clarify the underlying molecular mechanisms. PHF23 is overexpressed in NSCLC cell lines and tissues. High PHF23 levels correlate with short survival times and a poor response to chemotherapy in NSCLC patients. PHF23 overexpression facilitates cell proliferation, migration and sensitizes NSCLC cells to Cisplatin and Docetaxel by promoting DNA damage repair. Alpha-actinin-4 (ACTN4), as a downstream regulator, interacts with PHD domain of PHF23. Moreover, PHF23 is involved in ACTN4 stabilization by inhibiting its ubiquitination level. These results show that PHF23 plays an important role in the development and progression of NSCLC and suggest that PHF23 may serve as a therapeutic target in NSCLC patients.© 2023. The Author(s).