Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China.
Department of Medical Oncology, The First Hospital of China Medical University, Shenyang 110001, China; Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang 110001, China.
Exp Cell Res. 2018 Dec 15;373(1-2):180-187. doi: 10.1016/j.yexcr.2018.10.011. Epub 2018 Oct 25.
Although anti-programmed death ligand-1 (PD-L1) therapy has shown light in treatment of gastric cancer, only a limited number of patients respond to the treatment. In addition to its immunosuppressive effect, PD-L1 is involved in other functions of tumor cells. Previously study showed that PD-L1 promoted EMT in lung cancer cells. However, the other effect and role of PD-L1 in gastric cancer remains unclear. In the present study, we first demonstrated that PD-L1 promoted the proliferation and migration in gastric cancer cell lines. We found that another STAT family member, STAT5a, is involved in regulating the expression of PD-L1 in gastric cancer. Additionally, Cbl-b interacted and ubiquitated STAT5a, down-regulated the expression of STAT5a and PD-L1. Moreover, bioinformatics predictions and experimental data showed that Cbl-b is a target gene of the microRNA miR-940. We further found that miR-940 promoted the proliferation and migration of gastric cancer in vivo and in vitro. Taken together, our findings suggest that miR-940/Cbl-b/STAT5a axis regulated the expression of PD-L1, which promotes the proliferation and migration of gastric cancer cells.
尽管抗程序性死亡配体-1（PD-L1）治疗在胃癌治疗中显示出了曙光，但只有有限数量的患者对治疗有反应。除了其免疫抑制作用外，PD-L1 还参与肿瘤细胞的其他功能。先前的研究表明，PD-L1 促进了肺癌细胞中的 EMT。然而，PD-L1 在胃癌中的其他作用和角色尚不清楚。在本研究中，我们首先证明 PD-L1 促进了胃癌细胞系的增殖和迁移。我们发现另一个 STAT 家族成员 STAT5a 参与调节胃癌中 PD-L1 的表达。此外，Cbl-b 与 STAT5a 相互作用并泛素化 STAT5a，下调 STAT5a 和 PD-L1 的表达。此外，生物信息学预测和实验数据表明，Cbl-b 是 microRNA miR-940 的靶基因。我们进一步发现 miR-940 促进了胃癌在体内和体外的增殖和迁移。总之，我们的研究结果表明，miR-940/Cbl-b/STAT5a 轴调节 PD-L1 的表达，促进胃癌细胞的增殖和迁移。
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