TRIP suppresses cell proliferation and invasion in choroidal melanoma via promoting the proteasomal degradation of Twist1
TRIP suppresses cell proliferation and invasion in choroidal melanoma via promoting the proteasomal degradation of Twist1
复制标题
TRIP 通过促进 Twist1 蛋白酶体降解抑制脉络膜黑色素瘤细胞增殖和侵袭
DOI：
10.1002/1873-3468.13882
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发表时间：
2020-09-21
期刊：
影响因子：
3.5
通讯作者：
Zhang, Han
中科院分区：
文献类型：
--
作者：
Wei, Chao;Zhao, Xiaofei;Zhang, Han
脉络膜黑色素瘤（CM）仍然是最常见的眼内恶性肿瘤，受影响的患者的预后很差。虽然已知E3泛素连接酶TRAF相互作用蛋白（TRIP）在多种疾病中发挥关键调节作用，但其在CM中的相关性仍不确定。在本研究中，我们发现TRIP过表达在体外足以抑制CM细胞的增殖、侵袭和上皮-间质转化（EMT），而TRIP敲低后观察到相反的表型。我们进一步确定TRIP能够促进EMT相关转录因子Twist相关蛋白1的K48-聚泛素化，从而抑制EMT进展。总之，我们的研究结果表明，TRIP在调节CM的进展中起着重要作用，因此它可能是治疗这种疾病的重要治疗靶点。
Choroidal melanoma (CM) remains the most prevalent form of intraocular malignancy, and the prognosis of affected patients is poor. While the E3 ubiquitin ligase TRAF-interacting protein (TRIP) is known to play key regulatory roles in multiple diseases, its relevance in CM remains uncertain. In the present study, we found that TRIP overexpression is sufficient to inhibit the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of CM cellsin vitro, whereas the opposite phenotypes are observed following TRIP knockdown. We further determined that TRIP is able to promote the K48-polyubiquitination of EMT-associated transcription factor Twist-related protein 1, thereby suppressing EMT progression. Together, our results suggest that TRIP plays an important role in regulating the progression of CM and that it may therefore be an important therapeutic target for the treatment of this disease.