Department of Oncology, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Department of Radiology, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
J Int Med Res. 2024 Sep;52(9):3000605241271754. doi: 10.1177/03000605241271754.
Chaperonin containing TCP1 subunit 5 () encodes the CCT5 protein subunit of chaperonin-containing TCP-1 (CCT/TRiC) complex, and is shown to be upregulated in tumour pathogenesis. The study aim was to investigate the differential expression of between nasopharyngeal carcinoma (NPC) and noncancerous nasopharyngeal tissues, and the correlation between expression and clinicopathological parameters/prognosis in patients with NPC.
Microarray assay data were evaluated for differential expression between NPC and noncancerous nasopharyngeal tissues. expression in NPC and noncancerous nasopharyngeal tissues was determined at mRNA and protein levels by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Relationships between expression in NPC, clinical parameters, and prognosis were statistically analysed. CCT5-mediated cell proliferation was assessed using EdU and cell counting kit-8. Western blot and co-immunoprecipitation were utilized to explore E3 ubiquitin-protein ligase parkin (PARK2)-induced degradation of CCT5.
Microarray data showed CCT5 levels to be significantly increased in NPC versus noncancerous nasopharyngeal tissues, which was confirmed by qRT-PCR and immunohistochemical assays. Increased CCT5 protein levels positively correlated with tumour size, tumour recurrence, and clinical stage, and inversely correlated with patient's overall survival. Multivariate Cox regression analysis showed that enhanced CCT5 protein expression is an independent prognostic factor for patients with NPC. Overexpression of markedly induced NPC cell proliferation. Finally, PARK2, as a suppressive E3 ubiquitin-ligase enzyme, was shown to bind CCT5 and induce degradation in NPC.
Increased CCT5 may be an unfavourable factor promoting NPC growth. Binding of PARK2 to CCT5 was associated with CCT5 degradation, suggesting that PARK2 is an upstream negative modulator in NPC.
伴侣蛋白含有 TCP1 亚基 5() 编码伴侣蛋白含有 TCP-1 (CCT/TRiC) 复合物的 CCT5 蛋白亚基，并且在肿瘤发病机制中显示上调。本研究旨在探讨鼻咽癌细胞（NPC）与非癌性鼻咽组织之间的差异表达，并探讨 NPC 患者中表达与临床病理参数/预后的相关性。
通过微阵列分析评估 NPC 与非癌性鼻咽组织之间的差异表达。通过定量逆转录聚合酶链反应（qRT-PCR）和免疫组织化学法在 NPC 和非癌性鼻咽组织中测定 CCT5 的表达。统计学分析 CCT5 在 NPC 中的表达与临床参数和预后的关系。使用 EdU 和细胞计数试剂盒-8 评估 CCT5 介导的细胞增殖。利用 Western blot 和免疫共沉淀法探讨 E3 泛素蛋白连接酶 parkin (PARK2) 诱导的 CCT5 降解。
微阵列数据显示 CCT5 水平在 NPC 中明显高于非癌性鼻咽组织，qRT-PCR 和免疫组化检测结果也得到证实。CCT5 蛋白水平的升高与肿瘤大小、肿瘤复发和临床分期呈正相关，与患者的总生存率呈负相关。多变量 Cox 回归分析显示，增强的 CCT5 蛋白表达是 NPC 患者的独立预后因素。 过表达明显诱导 NPC 细胞增殖。最后，作为抑制性 E3 泛素连接酶的 PARK2，被证明与 CCT5 结合并诱导 NPC 中 CCT5 的降解。
CCT5 的增加可能是促进 NPC 生长的不利因素。PARK2 与 CCT5 的结合与 CCT5 的降解有关，表明 PARK2 是 NPC 的上游负调节因子。
