Department of Urology, Peking University People's Hospital, The Second Clinical Medical College of Peking University, Beijing 100044, China.
Department of Urology, Peking University People's Hospital, The Second Clinical Medical College of Peking University, Beijing 100044, China.
Life Sci. 2019 Sep 1;232:116614. doi: 10.1016/j.lfs.2019.116614. Epub 2019 Jun 28.
SRY-box 18 (SOX18) is a transcription factor known for its role in regulating cell differentiation and lymphatic and blood vessel development. It has been reported that SOX18 was involved in various diseases, including cancer. This study aimed to explore the significance and biological function of SOX18 in bladder cancer (BCa).
SOX18 expression in BCa and normal tissues was analyzed by immunohistochemistry, and SOX18 expression in BCa cell lines was quantified by western blotting and quantitative real-time PCR. The role of SOX18 on the proliferation, migration and invasion of BCa cells was explored by CCK-8 and transwell invasion assays in vitro. Cell cycle was measured by flow cytometry assays. Western blotting and qRT-PCR were performed to investigate the potential mechanisms by which SOX18 leads to tumor progression.
SOX18 was significantly upregulated in BCa and its expression was associated with clinical features of patients with BCa. Our data demonstrated that SOX18 promoted cell proliferation via accelerating cell cycle and by regulating c-Myc and Cyclin D1, promoted cell invasion via upregulation of MMP-7. Moreover, phosphorylation of c-Met and Akt regulated by SOX18 was identified to be involved in the process of cell migration and invasion, indicating the vital role of SOX18 in the metastasis of BCa.
Our data demonstrated a cancer-promoting effect of SOX18 in BCa, revealed the potential mechanisms of SOX18 in mediating cellular functions, and indicated that SOX18 may serve as a promising progression and prognostic biomarker and a therapeutic target for BCa.
SRY 框转录因子 18（SOX18）是一种已知的转录因子，其在调节细胞分化以及淋巴管和血管发育方面发挥作用。有报道称，SOX18 参与了多种疾病的发生，包括癌症。本研究旨在探讨 SOX18 在膀胱癌（BCa）中的意义和生物学功能。
采用免疫组织化学法分析 SOX18 在 BCa 组织和正常组织中的表达，采用 Western blot 和实时定量 PCR 法检测 SOX18 在 BCa 细胞系中的表达。体外采用 CCK-8 法和 Transwell 侵袭实验检测 SOX18 对 BCa 细胞增殖、迁移和侵袭的作用。采用流式细胞术检测细胞周期。Western blot 和 qRT-PCR 检测 SOX18 导致肿瘤进展的潜在机制。
SOX18 在 BCa 中显著上调，其表达与 BCa 患者的临床特征相关。我们的数据表明，SOX18 通过加速细胞周期和调节 c-Myc 和 Cyclin D1 促进细胞增殖，通过上调 MMP-7 促进细胞侵袭。此外，由 SOX18 调节的 c-Met 和 Akt 的磷酸化被鉴定为参与细胞迁移和侵袭的过程，表明 SOX18 在 BCa 的转移中起重要作用。
我们的数据表明 SOX18 在 BCa 中具有致癌作用，揭示了 SOX18 介导细胞功能的潜在机制，并表明 SOX18 可能作为 BCa 进展和预后的有前途的生物标志物和治疗靶点。
