Expression of the Annexin A1 gene is associated with suppression of growth, invasion and metastasis of nasopharyngeal carcinoma
Expression of the Annexin A1 gene is associated with suppression of growth, invasion and metastasis of nasopharyngeal carcinoma
复制标题
膜联蛋白 A1 基因的表达与抑制鼻咽癌的生长、侵袭和转移有关。
DOI：
10.3892/mmr.2014.2656
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发表时间：
2014-12-01
影响因子：
3.4
通讯作者：
Cheng, Ailan
中科院分区：
文献类型：
--
作者：
Liu, Aifeng;Huang, Weiguo;Cheng, Ailan
鼻咽癌（Nasopharyngeal carcinoma，NPC）在我国南方地区的发病率较高（20/100，000），而在世界其他地区则较为罕见。NPC是一种恶性肿瘤，因为它的高转移率;然而，有效诊断和治疗的生物标志物尚未确定。膜联蛋白A1是钙和磷脂结合蛋白大超家族中糖皮质激素调节的成员，已被证明在肿瘤发生和进展中具有重要作用，并被证明是头颈癌类型的预后生物标志物。本课题组前期的研究表明，Annexin A1在鼻咽癌组织中的表达较正常癌旁组织减少。为了研究Annexin A1是否是NPC的潜在生物标志物，本研究评估了Annexin A1对NPC生物学行为（即，高转移性NPC细胞系5 - 8 F和非转移性NPC细胞系6 - 10 B的侵袭和转移）。Western blot分析Annexin A1在上述两种细胞系中的表达水平。然后，使用重组质粒pEGFP-C1-Annexin A1和小干扰（si）RNA质粒pRNAT-U6.1-Annexin A1，并分别稳定转染5 - 8 F和6 - 10 B细胞。这些建立的重组细胞系，然后分别用于研究膜联蛋白A1的上调和下调。采用细胞增殖实验、流式细胞术、软琼脂集落形成实验、Transwell侵袭和迁移实验分析Annexin A1表达水平与鼻咽癌细胞系生物学行为的相关性。结果表明，上调Annexin A1表达可抑制鼻咽癌细胞的增殖、侵袭和迁移，下调Annexin A1表达可促进鼻咽癌细胞的增殖、侵袭和迁移。这些结果提示Annexin A1可能是NPC发生发展和预后的潜在生物标志物，其表达异常可能在其发病机制中起重要作用。
Nasopharyngeal carcinoma (NPC) has a highly increased incidence rate (20/100,000) in Southern regions of China, while being rare in the rest of the world. NPC is a malignant type of cancer due to its high occurrence rate of metastasis; however, biomarkers for effective diagnosis and treatment are yet to be identified. Annexin A1 is a glucocorticoid‑regulated member of a large superfamily of calcium and phospholipid‑binding proteins and has been shown to have important roles in tumor development and progression, and was demonstrated to be a prognostic biomarker for head and neck cancer types. A previous study by our group showed that Annexin A1 was decreased in NPC tissue as compared with normal adjacent tissue. To investigate whether Annexin A1 is a potential biomarker for NPC, the present study assessed the effect of the Annexin A1 on the biological behavior (i.e., invasion and metastasis) of the highly metastatic NPC cell line 5‑8F and the non‑metastatic NPC cell line 6‑10B. The expression levels of Annexin A1 in the above two cell lines were determined by western blot analysis. Next, the recombinant plasmid pEGFP‑C1‑Annexin A1 and the small interfering (si)RNA plasmid pRNAT‑U6.1‑Annexin A1 were used and stably transfected into 5‑8F and 6‑10B cells, respectively. These established recombinant cell lines were then used to study the up- and downregulation of Annexin A1, respectively. The correlation of Annexin A1 expression levels with the biological behavior of NPC cell lines was analyzed using a cell proliferation assay, flow cytometry, soft agar colony formation assay, as well as Transwell invasion and migration assays. The results demonstrated that upregulation of Annexin A1 suppressed the proliferation, invasion and migration of NPC cells, while downregulation of Annexin A1 promoted the proliferation, invasion and migration of NPC cells. These findings suggested that Annexin A1 may be a potential biomarker for the development and prognosis of NPC, and its dysregulation may have an important role in its underlying pathogenesis.