Department of ENT, Qingdao Central Hospital, Qingdao University, Qingdao, China.
Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6735-6743. doi: 10.26355/eurrev_202006_21661.
The purpose of this study was to investigate the expression level of EphA3 in nasopharyngeal carcinoma (NPC) and its effect on the proliferative capacity of NPC. Meanwhile, the underlying mechanism by which EphA3 prompts NPC malignant progression was further explored.
In this study, the expression of EphA3 in 42 pairs of tumor tissue specimens and paracancerous ones collected from NPC patients was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), and the interplay between EphA3 expression and clinical indicators, as well as prognosis of NPC patients was analyzed. Meanwhile, qRT-PCR was also applied to further verify EphA expression in NPC cell lines. In addition, EphA knockdown model was constructed in NPC cell lines, CNE2, and 6-10B, and the impacts of EphA on NPC cell functions was assessed through Cell Counting Kit-8 (CCK-8), cell colony formation, as well as 5-Ethynyl-2'- deoxyuridine (EdU) assays. Finally, a potential interplay between EphA3 and FOG2 was also investigated.
In this study, qRT-PCR results revealed that EphA3 expression levels in tumor tissues of patients with NPC were markedly higher than those in adjacent tissues. Compared with patients with low expression of EphA3, those with highly expressed EphA3 had a more advanced pathological stage. In addition, in vitro experiments showed that knocking down EphA3 notably attenuated the proliferation capacity of NPC cells. Subsequently, it was found that the expression of FOG2 in NPC cells was remarkably decreased both in NPC cell lines and tissues, which had a negative correlation with EphA3. Finally, cell recovery experiment revealed a mutual regulation between EphA3 and FOG2, which then together affected the malignant progression of NPC.
EphA3 is significantly relevant to pathological staging and poor prognosis of patients with NPC and may enhance the proliferation ability of NPC cells by modulating FOG2.
本研究旨在探讨 EphA3 在鼻咽癌(NPC)中的表达水平及其对 NPC 增殖能力的影响。同时,进一步探讨 EphA3 促使 NPC 恶性进展的潜在机制。
本研究通过定量实时聚合酶链反应(qRT-PCR)检测 42 对 NPC 患者肿瘤组织标本和癌旁组织标本中 EphA3 的表达,分析 EphA3 表达与 NPC 患者临床指标和预后的关系。同时,qRT-PCR 进一步验证 EphA 在 NPC 细胞系中的表达。此外,在 NPC 细胞系 CNE2 和 6-10B 中构建 EphA 敲低模型,通过细胞计数试剂盒-8(CCK-8)、细胞集落形成和 5-乙炔基-2'-脱氧尿苷(EdU)实验评估 EphA 对 NPC 细胞功能的影响。最后,还研究了 EphA3 与 FOG2 之间的潜在相互作用。
本研究通过 qRT-PCR 结果发现,NPC 患者肿瘤组织中 EphA3 的表达水平明显高于相邻组织。与 EphA3 低表达患者相比,EphA3 高表达患者的病理分期更晚。此外,体外实验表明,敲低 EphA3 显著减弱了 NPC 细胞的增殖能力。随后发现,NPC 细胞系和组织中 FOG2 的表达均明显降低,与 EphA3 呈负相关。最后,细胞恢复实验揭示了 EphA3 和 FOG2 之间的相互调节作用,它们共同影响 NPC 的恶性进展。
EphA3 与 NPC 患者的病理分期和预后不良显著相关,可能通过调节 FOG2 增强 NPC 细胞的增殖能力。