锌指蛋白 148 (ZNF-148) 在大多数人类癌症病理生理学中的影响已有报道；然而，ZNF-148在乳腺癌中的生物学功能仍不清楚。本研究旨在阐明ZNF-148在乳腺癌病理学中的潜在分子机制。在乳腺癌组织和细胞中检测了ZNF148的表达。然后，用ZNF-148过表达或下调载体转染细胞，并分别通过MTT、western blot、流式细胞术和免疫荧光染色分析细胞增殖、焦亡、凋亡和活性氧（ROS）产生。使用荷瘤裸鼠评价ZNF-148的肿瘤发生。使用生物信息学和荧光素酶测定检查了 ZNF-148 的作用机制。我们发现 ZNF-148 在乳腺癌组织和细胞系中表达上调。 ZNF-148 的敲低可抑制恶性表型，包括体外和体内的细胞增殖、上皮间质转化和肿瘤发生，而 ZNF-148 过表达则具有相反的作用。进一步的实验表明，ZNF-148 缺陷促进 ROS 产生并引发细胞凋亡和焦亡细胞死亡，通过用 ROS 清除剂共同处理细胞可以恢复这种死亡。荧光素酶报告基因检测显示，miR-335 是 ZNF-148 的下游靶标，过表达的 ZNF-148 通过海绵 miR-335 增加超氧化物歧化酶 2 (SOD2) 的表达。与此同时，miR-335 下调和 SOD2 过表达消除了 ZNF-148 缺乏对乳腺癌细胞增殖和细胞焦亡的抗肿瘤作用。我们的研究结果表明，ZNF-148 通过触发 miR-335/SOD2/ROS 促进乳腺癌进展。介导焦亡细胞死亡并帮助识别乳腺癌的潜在治疗靶点。© 2023 作者。约翰·威利出版的癌症医学

The implication of zinc finger protein 148 (ZNF-148) in pathophysiology of most human cancers has been reported; however, the biological functions of ZNF-148 in breast cancer remain unclear. This study sought to elucidate the potential molecular mechanism of ZNF-148 on breast cancer pathology.ZNF148 expression was tested in breast cancer tissues and cells. Then, cells were transfected with ZNF-148 overexpression or downregulation vector, and the cell proliferation, pyroptosis, apoptosis, and reactive oxygen species (ROS) production were analyzed by MTT, western blot, flow cytometry, and immunofluorescence staining, respectively. Tumor-bearing nude mouse was used to evaluate tumorigenesis of ZNF-148. Mechanisms underpinning ZNF-148 were examined using bioinformatics and luciferase assays.We found that ZNF-148 was upregulated in breast cancer tissues and cell lines. Knockdown of ZNF-148 suppressed malignant phenotypes, including cell proliferation, epithelial-mesenchymal transition, and tumorigenesis in vitro and in vivo, while ZNF-148 overexpression had the opposite effects. Further experiments showed that ZNF-148 deficiency promoted ROS production and triggered both apoptotic and pyroptotic cell death, which were restored by cotreating cells with ROS scavengers. A luciferase reporter assay revealed that miR-335 was the downstream target of ZNF-148 and that overexpressed ZNF-148 increased superoxide dismutase 2 (SOD2) expression by sponging miR-335. In parallel, both miR-335 downregulation and SOD2 overexpression abrogated the antitumor effects of ZNF-148 deficiency on proliferation and pyroptosis in breast cancer cells.Our findings indicated that ZNF-148 promotes breast cancer progression by triggering miR-335/SOD2/ROS-mediated pyroptotic cell death and aid the identification of potential therapeutic targets for breast cancer.© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.