DEPDC1B通過UBE2T介導的BIRC5泛素化調控人脊索瘤的進展

2021年8月，首都醫(yī)科大學北京天壇醫(yī)院神經外科；上海交通大學醫(yī)學院銅仁醫(yī)院骨科；上海交通大學醫(yī)學院仁濟醫(yī)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老師研究團隊在《Cell Death & Disease》上發(fā)表論文：

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

“DEPDC1B通過UBE2T介導的BIRC5泛素化調控人脊索瘤的進展”

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：

脊索瘤是一種罕見的骨惡性腫瘤，具有很高的局部復發(fā)和遠處轉移率。盡管DEP結構域蛋白1B (DEPDC1B)與多種惡性腫瘤有關，但其與脊索瘤的關系尚不清楚。本研究探討DEPDC1B在脊索瘤中的生物學作用及分子機制。通過體外和體內功能缺失實驗，闡明了DEPDC1B在脊索瘤細胞中的功能。此外，通過RNA測序和Co-Immunoprecipitation (Co-IP)實驗，我們進一步確定了DEPDC1B在脊索瘤細胞中的分子機制。敲低DEPDC1B的脊索瘤細胞的惡性行為明顯受到抑制，表現為增殖減少、凋亡增強、遷移受阻。在異種移植小鼠中，降低DEPDC1B的表達可以抑制腫瘤的生長。從機制上講，DEPDC1B通過泛素偶聯酶E2T (UBE2T)影響了桿狀病毒細胞凋亡重復物抑制劑5 (BIRC5)的泛素化。同時下調BIRC5和DEPDC1B可能加劇脊索瘤的抑制作用。此外，BIRC5過表達降低了DEPDC1B在脊索瘤細胞中的抑制作用。綜上所述，DEPDC1B通過ube2t介導的BIRC5泛素化調控人脊索瘤的進展，提示它可能是一個有潛在治療價值的候選靶點。

該論文中，人脊索瘤細胞系U-CH1和MUG-Chor1細胞的體外培養(yǎng)是使用Ausbian特級胎牛血清完成的。欲了解或購買Ausbian特級胎牛血清可以聯系北京締一生物400-166-8600.