Department of Otolaryngology/Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
Oncol Res. 2018 Jan 19;26(1):111-122. doi: 10.3727/096504017X14924753593574. Epub 2017 Apr 18.
This study aimed to investigate the clinical significance of cullin 3 expression in nasopharyngeal carcinoma (NPC), as well as to explore the regulatory mechanism of cullin 3 underlying the growth and metastasis of NPC cells. Our findings showed that the expression levels of cullin 3 were significantly increased in both NPC tissues and cell lines. A strong positive correlation was found between cullin 3 expression and the Ki-67-based proliferation index in NPC tissues. Moreover, cullin 3 overexpression was correlated with local relapse and distant metastasis in NPC patients. In vitro experiments showed that knockdown of cullin 3 caused a significant reduction in the proliferation of NPC cells, probably by inducing cell cycle arrest. In addition, downregulation of cullin 3 inhibited colony formation and the migratory and invasive capacities of NPC cells. The expression levels of PCNA and epithelial-to-mesenchymal transition (EMT)-related proteins were also meditated by cullin 3 in NPC cells. Based on these findings, we demonstrated that cullin 3 plays a promoting role in the malignant progression of NPC and suggest that the cullin 3-based ubiquitin proteasome pathway may be used as a promising therapeutic target for NPC.
本研究旨在探讨 Cullin 3 在鼻咽癌（NPC）中的临床意义，并探索 Cullin 3 调控 NPC 细胞生长和转移的机制。我们的研究结果表明，Cullin 3 的表达水平在 NPC 组织和细胞系中均显著升高。在 NPC 组织中，Cullin 3 表达与 Ki-67 增殖指数呈强正相关。此外，Cullin 3 过表达与 NPC 患者局部复发和远处转移相关。体外实验表明，Cullin 3 敲低可显著抑制 NPC 细胞的增殖，可能通过诱导细胞周期停滞。此外，下调 Cullin 3 可抑制 NPC 细胞的集落形成和迁移侵袭能力。PCNA 和上皮间质转化（EMT）相关蛋白的表达也受 NPC 细胞中 Cullin 3 的调节。基于这些发现，我们证明 Cullin 3 在 NPC 的恶性进展中发挥促进作用，并提示 Cullin 3 介导的泛素蛋白酶体途径可能成为 NPC 有前途的治疗靶点。
