Department of Oral Surgery, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
Department of Endodontics, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.
Oncol Rep. 2019 Mar;41(3):1749-1758. doi: 10.3892/or.2019.6974. Epub 2019 Jan 22.
Regional and distant metastases are the principal reasons underlying the high mortality rate associated with tongue squamous cell carcinoma (TSCC); however, the precise molecular mechanisms involved in tongue tumorigenesis remain unknown. The present study aimed to determine the expression and mechanism of regulation of Wnt7a in the growth and metastasis of TSCC. Wnt7a mRNA and protein expression levels were examined in TSCC tissues using reverse transcription‑quantitative polymerase chain reaction and immunohistochemical staining. A loss‑of‑function assay was performed in TSCC cell lines using Wnt7a small interfering RNA or short hairpin RNA, after which, cell proliferation, migration and invasion were analyzed using Cell Counting Kit‑8, tumorigenicity and Transwell assays, respectively. Epithelial‑mesenchymal transition (EMT)‑associated proteins were detected by western blotting. The mRNA and protein expression levels of Wnt7a were significantly upregulated in cancer tissues compared with in the adjacent non‑cancerous tissues. Clinical analysis indicated that Wnt7a expression was associated with T classification, lymph node metastasis and pathological differentiation, and high Wnt7a expression predicted a short recurrence‑free survival for patients with TSCC. Silencing Wnt7a expression suppressed cell proliferation, migration and invasion, and reversed the EMT phenotype in TSCC cell lines. The present study revealed that Wnt7a may be upregulated in TSCC, where it may participate in modulating cell proliferation, migration, invasion and the EMT of TSCC. Therefore, Wnt7a should be considered a novel oncogene, and a potential prognostic and therapeutic target for patients with TSCC.
区域和远处转移是导致舌鳞状细胞癌(TSCC)高死亡率的主要原因;然而,舌肿瘤发生的确切分子机制尚不清楚。本研究旨在确定 Wnt7a 在 TSCC 生长和转移中的表达和调控机制。采用逆转录-定量聚合酶链反应和免疫组织化学染色检测 TSCC 组织中 Wnt7a mRNA 和蛋白的表达水平。在 TSCC 细胞系中采用 Wnt7a 小干扰 RNA 或短发夹 RNA 进行功能丧失实验,然后分别采用细胞计数试剂盒-8、肿瘤形成和 Transwell 实验分析细胞增殖、迁移和侵袭。采用 Western blot 检测上皮-间充质转化(EMT)相关蛋白。与相邻非癌组织相比,癌症组织中 Wnt7a 的 mRNA 和蛋白表达水平明显上调。临床分析表明,Wnt7a 的表达与 T 分类、淋巴结转移和病理分化有关,Wnt7a 高表达预示着 TSCC 患者的无复发生存期较短。沉默 Wnt7a 表达抑制了 TSCC 细胞系中的细胞增殖、迁移和侵袭,并逆转了 EMT 表型。本研究表明,Wnt7a 可能在 TSCC 中上调,可能参与调节 TSCC 的细胞增殖、迁移、侵袭和 EMT。因此,Wnt7a 可被视为一种新的癌基因,有望成为 TSCC 患者的一种潜在预后和治疗靶点。