Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Biochem Biophys Res Commun. 2021 Apr 9;548:53-59. doi: 10.1016/j.bbrc.2021.02.056. Epub 2021 Feb 22.
Lung cancer is the leading cause of cancer-related deaths worldwide. Lung cancer stem cells (CSCs) are a small population of cancer cells with self-renewal, therapeutic resistance, and tumor relapse capability. Yet the molecular mechanisms underlying lung CSCs self-renewal remain largely unknown. Here, we report that SH3BGRL were down-regulated in lung cancer tissues comparing with normal lung tissues and SH3BGRL low expression was correlated with the poor clinical outcomes of patients with lung cancer. Moreover, SH3BGRL was also weakly expressed in lung CSCs compared with its corresponding lung cancer cells. We first characterize that EZH2 directly binds to SH3BGRL promoter and transcriptional represses SH3BGRL expression in epigenetic level. Functionally, overexpression of SH3BGRL potently suppresses Lung CSCs self-renewal in vitro. The gain of function study reveals that SH3BGRL acts as a novel tumor suppressor via inhibiting lung cancer cell proliferation and migration as well as Lung CSCs self-renewal in vitro. Collectively, our work demonstrates that SH3BGRL hold potential as a favorable prognostic marker and therapeutic target for patients with lung cancer in future.
肺癌是全球癌症相关死亡的主要原因。肺癌干细胞（CSCs）是一小群具有自我更新、治疗抵抗和肿瘤复发能力的癌细胞。然而，肺癌 CSCs 自我更新的分子机制在很大程度上仍不清楚。在这里，我们报告说，与正常肺组织相比，SH3BGRL 在肺癌组织中表达下调，并且 SH3BGRL 低表达与肺癌患者的不良临床结局相关。此外，与相应的肺癌细胞相比，SH3BGRL 在肺癌 CSCs 中也表达较弱。我们首先确定 EZH2 直接结合到 SH3BGRL 启动子上，并在表观遗传水平上转录抑制 SH3BGRL 的表达。功能上，SH3BGRL 的过表达在体外强烈抑制肺癌 CSCs 的自我更新。功能获得研究表明，SH3BGRL 通过抑制肺癌细胞增殖、迁移以及体外肺癌 CSCs 自我更新，作为一种新型肿瘤抑制因子发挥作用。总之，我们的工作表明，SH3BGRL 有望成为未来肺癌患者的有利预后标志物和治疗靶点。
