Cancer Center, Jiangsu Shengze Hospital of Nanjing Medical University, Jiangsu, Suzhou, China.
Department of Ultrasound, Jiangsu Shengze Hospital of Nanjing Medical University, Jiangsu, Suzhou, China.
Bioengineered. 2022 Jan;13(1):107-118. doi: 10.1080/21655979.2021.2009411.
Colorectal cancer (CRC) is a common malignancy of the gastrointestinal tract, which has the second highest incidence among gastrointestinal tumors. At present, due to the limitations of current CRC treatment strategies, there is an urgent need for developing more effective therapies. B7 family member H4 (B7-H4) is associated with the progression of a wide spectrum of cancers, but its functional role in CRC is unknown. The purpose of this study is to clarify the role of B7-H4 in CRC and the underlying mechanisms in controlling the progression of CRC. Our data showed that B7-H4 expression in CRC tissues and cell lines was significantly upregulated as compared with normal tissues and normal cell lines. High B7-H4 expression was correlated with a poor prognosis of CRC patients. B7-H4 overexpression promoted the proliferation and invasion of CRC cells, which could be suppressed by Wnt signaling inhibitor. In a mouse xenograft model, silencing B7-H4 suppressed tumor growth and epithelial-mesenchymal transition (EMT) of CRC cells. Collectively, our study demonstrated the oncogenic roles of B7-H4 in regulating the proliferation, EMT as well as the migration of CRC cells through Wnt signaling pathway. The heightened expression of B7-H4 could serve as a prognostic marker for CRC patients.
结直肠癌（CRC）是一种常见的胃肠道恶性肿瘤，其在胃肠道肿瘤中的发病率居第二位。目前，由于CRC 治疗策略的局限性，迫切需要开发更有效的治疗方法。B7 家族成员 H4（B7-H4）与广泛谱的癌症进展有关，但它在 CRC 中的功能作用尚不清楚。本研究旨在阐明 B7-H4 在 CRC 中的作用及其在控制 CRC 进展中的潜在机制。我们的数据显示，CRC 组织和细胞系中 B7-H4 的表达明显高于正常组织和正常细胞系。高 B7-H4 表达与 CRC 患者的预后不良相关。B7-H4 的过表达促进了 CRC 细胞的增殖和侵袭，而 Wnt 信号抑制剂可抑制其增殖和侵袭。在小鼠异种移植模型中，沉默 B7-H4 可抑制 CRC 细胞的肿瘤生长和上皮间质转化（EMT）。总之，我们的研究表明，B7-H4 通过 Wnt 信号通路调节 CRC 细胞的增殖、EMT 以及迁移，从而发挥致癌作用。B7-H4 的高表达可作为 CRC 患者的预后标志物。
