School of Stomatology, China Medical University, Shenyang 110002, P.R. China.
Department of Immunology, School of Basic Medical Science, China Medical University, Shenyang 110002, P.R. China.
Mol Med Rep. 2017 Oct;16(4):4569-4576. doi: 10.3892/mmr.2017.7214. Epub 2017 Aug 10.
Ras-related protein Rab-5A (Rab5a) has been identified to be overexpressed in several types of human cancer. However, its clinical significance and biological roles in oral cancer remain unclear. In the present study, the protein expression of Rab5a was examined in 79 cases of oral squamous cell carcinoma samples using immunohistochemistry. It was demonstrated that Rab5a protein was upregulated in 49.3% (39/79) of cancer samples. Small interfering RNA knockdown was performed on Detroit 562 cells with high endogenous expression. Rab5a transfection was performed in FaDu cells with low endogenous levels. Rab5a depletion was revealed to inhibit cell growth, invasion and colony formation while its overexpression facilitated cell growth, invasion, and colony formation. In addition, Rab5a facilitated cell cycle progression and cell migration. It was also demonstrated that Rab5a depletion downregulated and its overexpression upregulated the expression levels of various cell cycle‑associated proteins, and matrix metalloproteinase‑2 (MMP‑2). Furthermore, Rab5a positively regulated the extracellular signal‑regulated kinase (ERK) signaling pathway and promoted epithelial‑mesenchymal transition (EMT). ERK inhibitor PD98059 partially inhibited the role of Rab5a on MMP‑2, cyclin D1, cell proliferation and invasion. The results of the present study suggest that Rab5a is overexpressed in oral cancer tissue samples and promotes the malignant phenotype through EMT and the ERK/MMP‑2 signaling pathway.
Ras 相关蛋白 Rab-5A（Rab5a）已被鉴定在几种人类癌症中过表达。然而，其在口腔癌中的临床意义和生物学作用尚不清楚。在本研究中，通过免疫组织化学法检测了 79 例口腔鳞状细胞癌样本中 Rab5a 蛋白的表达。结果表明，在 49.3%（39/79）的癌症样本中 Rab5a 蛋白上调。用小干扰 RNA 敲低 Detroit 562 细胞中高内源性表达的 Rab5a。在低内源性水平的 FaDu 细胞中转染 Rab5a。结果显示，Rab5a 耗竭抑制细胞生长、侵袭和集落形成，而过表达则促进细胞生长、侵袭和集落形成。此外，Rab5a 促进细胞周期进程和细胞迁移。还表明，Rab5a 耗竭下调，而过表达上调各种细胞周期相关蛋白和基质金属蛋白酶-2（MMP-2）的表达水平。此外，Rab5a 正向调节细胞外信号调节激酶（ERK）信号通路并促进上皮-间充质转化（EMT）。ERK 抑制剂 PD98059 部分抑制了 Rab5a 对 MMP-2、细胞周期蛋白 D1、细胞增殖和侵袭的作用。本研究结果表明，Rab5a 在口腔癌组织样本中过表达，并通过 EMT 和 ERK/MMP-2 信号通路促进恶性表型。
