Imoto Tomoko, Kondo Satoru, Wakisaka Naohiro, Hai Pham Tahnh, Seishima Noriko, Kano Makoto, Ueno Takayoshi, Mizokami Harue, Nakanishi Yosuke, Hatano Miyako, Endo Kazuhira, Sugimoto Hisashi, Moriyama-Kita Makiko, Yoshizaki Tomokazu
Division of Otolaryngology and Head and Neck Surgery, Graduate School of Medical Science, Kanazawa University, 13-1 Takara, Kanazawa, Ishikawa 920-8641, Japan.
Microorganisms. 2020 Mar 17;8(3):423. doi: 10.3390/microorganisms8030423.
Semaphorins were discovered as guidance signals that mediate neural development. Recent studies suggest that semaphorin 3A (Sema3A), a member of the semaphorin family, is involved in the development of several cancers. This study aimed to analyze the association of Sema3A with the clinical features of nasopharyngeal carcinoma (NPC), an Epstein-Barr virus-associated carcinoma, and the Epstein-Barr virus primary oncogene latent membrane protein 1 (LMP1). The expression of Sema3A and LMP1 was immunohistochemically examined in the 35 NPC specimens. The mean expression scores for Sema3A and LMP1 were 20.8% ± 14.5% and 13.9% ± 14.8%, respectively. The expression of Sema3A significantly correlated with that of LMP1 (r = 0.41, = 0.014). In addition, the Sema3A high cohort showed significantly poorer prognosis than the Sema3A low cohort. Sema3A expression was higher in the LMP1-positive KH-1 and KR-4 cell lines compared to the LMP1-negative HeLa cells. Overexpression of LMP1 in the LMP1-negative AdAH cell line upregulated Sema3A expression, both at the transcriptional and translational level. Finally, Sema3A expression was associated with poor prognosis in patients with NPC. Our data suggest that LMP1 induces the expression of Sema3A, which may promote tumor progression in NPC.
信号素最初被发现是介导神经发育的导向信号。最近的研究表明，信号素家族成员之一的信号素3A（Sema3A）与多种癌症的发生发展有关。本研究旨在分析Sema3A与鼻咽癌（NPC，一种与爱泼斯坦-巴尔病毒相关的癌症）的临床特征以及爱泼斯坦-巴尔病毒原癌基因潜伏膜蛋白1（LMP1）之间的关联。采用免疫组织化学方法检测了35例NPC标本中Sema3A和LMP1的表达情况。Sema3A和LMP1的平均表达评分分别为20.8%±14.5%和13.9%±14.8%。Sema3A的表达与LMP1的表达显著相关（r = 0.41，P = 0.014）。此外，Sema3A高表达组的预后明显比Sema3A低表达组差。与LMP1阴性的HeLa细胞相比，LMP1阳性的KH-1和KR-4细胞系中Sema3A的表达更高。在LMP1阴性的AdAH细胞系中过表达LMP1，在转录和翻译水平上均上调了Sema3A的表达。最后，Sema3A的表达与NPC患者的不良预后相关。我们的数据表明，LMP1诱导Sema3A的表达，这可能促进NPC的肿瘤进展。
