Han Ming-Zhi, Huang Bin, Chen An-Jing, Zhang Xin, Xu Ran, Wang Jian, Li Xin-Gang
Department of Neurosurgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Rep. 2017 Feb;37(2):903-912. doi: 10.3892/or.2017.5349. Epub 2017 Jan 3.
The Ras-related GTP-binding protein (RAB) family plays an important role in regulating signal transduction and cellular processes including vesicle transport, cytoskeleton formation and membrane trafficking. More recently, several RAB members have been reported to promote tumorigenesis in many types of cancers. However, the clinical significance and potential function of RAB43 in gliomas remain unclear. Herein, we found that RAB43 was upregulated and positively correlated with the grade of progression in glioma patients by in silico analysis and immunohistochemistry (IHC). Patients with high RAB43 displayed worse clinical outcomes in comparison to those with low RAB43. RAB43 was also highly expressed in mesenchymal and G3 subtypes, and isocitrate dehydrogenase 1 (IDH1) wild-type gliomas. Moreover, transcriptomic analyses via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that RAB43‑related gene sets were mainly involved in the regulation of cell adhesion and cell migration processes. Further investigation indicated that RAB43 downregulation significantly suppressed the migratory and invasive ability of glioma cells, as well as decreased the expression of epithelial-mesenchymal transition (EMT) markers (N-cadherin, vimentin and Snail). In conclusion, a high level of RAB43 was significantly associated with the malignant phenotypes of gliomas, which suggests that RAB43 may serve as a novel biomarker and a potential therapeutic target for gliomas.
Ras相关GTP结合蛋白（RAB）家族在调节信号转导和细胞过程中发挥重要作用，这些过程包括囊泡运输、细胞骨架形成和膜运输。最近，有报道称几个RAB成员在多种癌症中促进肿瘤发生。然而，RAB43在胶质瘤中的临床意义和潜在功能仍不清楚。在此，我们通过电子分析和免疫组织化学（IHC）发现，RAB43在胶质瘤患者中上调，且与疾病进展程度呈正相关。与RAB43低表达的患者相比，RAB43高表达的患者临床预后更差。RAB43在间充质和G3亚型以及异柠檬酸脱氢酶1（IDH1）野生型胶质瘤中也高表达。此外，通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路进行的转录组分析表明，RAB43相关基因集主要参与细胞黏附和细胞迁移过程的调控。进一步研究表明，RAB43下调显著抑制胶质瘤细胞的迁移和侵袭能力，并降低上皮-间质转化（EMT）标志物（N-钙黏蛋白、波形蛋白和Snail）的表达。总之，高水平的RAB43与胶质瘤的恶性表型显著相关，这表明RAB43可能作为一种新的生物标志物和胶质瘤的潜在治疗靶点。
