DEPDC1B通过UBE2T介导的BIRC5泛素化调控人脊索瘤的进展

2021年8月，首都医科大学北京天坛医院神经外科；上海交通大学医学院铜仁医院骨科；上海交通大学医学院仁济医院骨科(Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 Nansihuan Xilu, Beijing 100070, China；Department of Orthopaedic Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111 Xianxia Road, Shanghai 200336, China；Department of Orthopaedic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, No. 2000 Jiangyue Road, Shanghai 200127, China) Zhen Wu老师研究团队在《Cell Death & Disease》上发表论文：

“DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5”

“DEPDC1B通过UBE2T介导的BIRC5泛素化调控人脊索瘤的进展”

Abstract：

Chordoma is a rare bone malignancy with a high rate of local recurrence and distant metastasis. Although DEP domain-containing protein 1B (DEPDC1B) is implicated in a variety of malignancies, its relationship with chordoma is unclear. In this study, the biological role and molecular mechanism of DEPDC1B in chordoma were explored. The function of DEPDC1B in chordoma cells was clarified through loss-of-function assays in vitro and in vivo. Furthermore, molecular mechanism of DEPDC1B in chordoma cells was recognized by RNA sequencing and Co-Immunoprecipitation (Co-IP) assay. The malignant behaviors of DEPDC1B knockdown chordoma cells was significantly inhibited, which was characterized by reduced proliferation, enhanced apoptosis, and hindered migration. Consistently, decreased expression of DEPDC1B suppressed tumor growth in xenograft mice. Mechanically, DEPDC1B affected the ubiquitination of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) through ubiquitin-conjugating enzyme E2T (UBE2T). Simultaneous downregulation of BIRC5 and DEPDC1B may exacerbate the inhibitory effects of chordoma. Moreover, BIRC5 overexpression reduced the inhibitory effects of DEPDC1B knockdown in chordoma cells. In conclusion, DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5, suggesting that it may be a promising candidate target with potential therapeutic value.

摘要：

脊索瘤是一种罕见的骨恶性肿瘤，具有很高的局部复发和远处转移率。尽管DEP结构域蛋白1B (DEPDC1B)与多种恶性肿瘤有关，但其与脊索瘤的关系尚不清楚。本研究探讨DEPDC1B在脊索瘤中的生物学作用及分子机制。通过体外和体内功能缺失实验，阐明了DEPDC1B在脊索瘤细胞中的功能。此外，通过RNA测序和Co-Immunoprecipitation (Co-IP)实验，我们进一步确定了DEPDC1B在脊索瘤细胞中的分子机制。敲低DEPDC1B的脊索瘤细胞的恶性行为明显受到抑制，表现为增殖减少、凋亡增强、迁移受阻。在异种移植小鼠中，降低DEPDC1B的表达可以抑制肿瘤的生长。从机制上讲，DEPDC1B通过泛素偶联酶E2T (UBE2T)影响了杆状病毒细胞凋亡重复物抑制剂5 (BIRC5)的泛素化。同时下调BIRC5和DEPDC1B可能加剧脊索瘤的抑制作用。此外，BIRC5过表达降低了DEPDC1B在脊索瘤细胞中的抑制作用。综上所述，DEPDC1B通过ube2t介导的BIRC5泛素化调控人脊索瘤的进展，提示它可能是一个有潜在治疗价值的候选靶点。

该论文中，人脊索瘤细胞系U-CH1和MUG-Chor1细胞的体外培养是使用Ausbian特级胎牛血清完成的。欲了解或购买Ausbian特级胎牛血清可以联系北京缔一生物400-166-8600.