Xu Liang, Mo Yejia, Yu Bingqi, Fan Sunfu
General Surgery Department, Zhejiang Hospital, No.1229 Gudun Road, Xihu, Hangzhou, 310013, Zhejiang, China.
Neurology Department, Zhejiang Hospital, Hangzhou, 310013, Zhejiang, China.
Discov Oncol. 2025 Jul 28;16(1):1419. doi: 10.1007/s12672-025-03157-z.
Colorectal cancer (CRC) ranks as one of the most malignant solid tumors worldwide. Bromodomain containing 8 (BRD8) functions as an oncogene in various cancers. This study aimed to investigate the roles of BRD8 in CRC. mRNA expression was detected using reverse transcription-quantitative PCR (RT-qPCR). Protein expression was detected using Western blot. The expression of macrophage markers was detected using immunohistochemistry and immunofluorescence. Cell viability was detected using Cell Counting Kit-8 (CCK-8) assay. Macrophage function was detected using flow cytometry. Cell migration and invasion was detected using transwell assays. We found that high levels of BRD8 mediated the predominance of M2-like tumor-associated macrophages (TAM2) and predicted poor prognosis of CRC patients. However, BRD8 knockdown suppressed TAM2 polarization as well as the migration and invasion of CRC cells. Mechanically, BRD8-mediated the upregulation of transforming growth factor β1 (TGF-β1), overexpression of which promoted TAM2 polarization and aggressiveness of CRC cells. Taken together, BRD8 deficiency suppressed TAM2 polarization, inhibiting the progression of CRC. Therefore, BRD8 may be a therapeutic target for CRC.
结直肠癌（CRC）是全球最恶性的实体瘤之一。含溴结构域8（BRD8）在多种癌症中作为癌基因发挥作用。本研究旨在探讨BRD8在结直肠癌中的作用。采用逆转录定量PCR（RT-qPCR）检测mRNA表达。采用蛋白质印迹法检测蛋白质表达。采用免疫组织化学和免疫荧光法检测巨噬细胞标志物的表达。采用细胞计数试剂盒8（CCK-8）检测细胞活力。采用流式细胞术检测巨噬细胞功能。采用Transwell实验检测细胞迁移和侵袭。我们发现，高水平的BRD8介导了M2样肿瘤相关巨噬细胞（TAM2）的优势，并预示着CRC患者的预后不良。然而，BRD8基因敲低抑制了TAM2极化以及CRC细胞的迁移和侵袭。机制上，BRD8介导转化生长因子β1（TGF-β1）的上调，其过表达促进了TAM2极化和CRC细胞的侵袭性。综上所述，BRD8缺陷抑制了TAM2极化，抑制了结直肠癌的进展。因此，BRD8可能是结直肠癌的治疗靶点。
