RAB26通过激活β-catenin信号促进鼻咽癌细胞增殖

RAB26 Promotes Nasopharyngeal Carcinoma Cell Proliferation through Activation of β-catenin Signaling

该文探讨了RAB26对鼻咽癌细胞增殖的影响及其机制。采用实时荧光定量PCR和免疫组织化学实验检测鼻咽癌组织及正常鼻咽上皮组织RAB26 mRNA和蛋白表达水平,并将免疫组织化学方法检测的RAB26表达水平与患者临床病理特征进行统计分析。在鼻咽癌CNE-2细胞过表达RAB26、在HNE1细胞敲降RAB26,分别建立过表达以及敲降细胞系。利用CCK-8增殖实验、细胞克隆形成实验及EdU增殖实验检测过表达和敲降RAB26对鼻咽癌细胞增殖的影响;Western blot检测过表达和敲降RAB26的鼻咽癌细胞RAB26,Wnt/β-catenin信号中的β-catenin、cyclin D1、c-Myc、survivin的蛋白水平及MAPK/ERK信号中的p-p38 MAPK/p38 MAPK、p-ERK/ERK的蛋白水平。细胞克隆形成实验检测CNE-2过表达RAB26细胞经不同照射剂量(0 Gy、2 Gy、4 Gy、6 Gy及8 Gy)X射线照射后的细胞活力。结果显示,RAB26在鼻咽癌中高表达;RAB26在鼻咽癌中的表达水平与肿瘤类型(r=0.294,P<0.05)和转移/复发(r=0.290,P<0.05)呈正相关;过表达RAB26后,CNE-2鼻咽癌细胞增殖加快,β-catenin、cyclin D1、c-Myc、survivin蛋白表达水平增加,p-p38 MAPK、p-ERK蛋白表达水平明显增高;敲低RAB26后则相反;过表达RAB26会降低鼻咽癌细胞的放射敏感性。综上,RAB26在鼻咽癌中高表达,并通过激活Wnt/β-catenin信号通路和MAPK/ERK信号通路促进鼻咽癌细胞增殖。

This study explored the effect of RAB26 on nasopharyngeal carcinoma cell proliferation and its underlying mechanism.The RAB26 mRNA and protein expression levels in nasopharyngeal cancer tissues and normal nasopharyngeal epithelial tissues were detected by real-time fluorescence quantitative PCR and immuno-histochemistry experiments,and statistical analyses of RAB26 expression levels evaluated by immunohistochem-istry with the clinicopathological characteristics of patients.RAB26 was overexpressed in nasopharyngeal carcinoma CNE-2 cells and knocked down in HNE1 cells,and overexpressed and knocked down cell lines were established respectively.The impact of RAB26 on the proliferation of the NPC cells was detected by CCK-8 proliferation assay,cell clone formation assay and EdU proliferation assay.Western blot assay was used to detect the protein expression levels of RAB26,β-catenin,cyclinD1,c-Myc and survivin in Wnt/β-catenin signaling and p-p38 MAPK/p38 MAPK,p-ERK/ERK in MAPK/ERK signaling in nasopharyngeal carcinoma cells with overexpression and knockdown of RAB26.The CNE-2 overexpressed RAB26 cell viability after X-ray irradiation with different irradiation doses(0 Gy,2 Gy,4 Gy,6 Gy and 8 Gy)was detected in the cell clone formation assay.The results showed that RAB26 was highly expressed in naso-pharyngeal carcinoma.The expression level of RAB26 in nasopharyngeal carcinoma was positively correlated with the tumor type(r=0.294,P<0.05)and metastasis/recurrence(r=0.290,P<0.05).After overexpression of RAB26,CNE-2 nasopharyngeal carcinoma cells showed accelerated proliferation,increased expression ofβ-catenin,cyclin D1,c-Myc,and survivin proteins,and increased expression of p-p38 MAPK,p-ERK proteins,while the opposite was observed after knockdown of RAB26.Reduced radiosensitivity of nasopharyngeal carcinoma cells by overexpres-sion of RAB26.In conclusion,RAB26 showed high expression in nasopharyngeal carcinoma and promoted the pro-liferation of nasopharyngeal carcinoma cells by activating the Wnt/β-catenin signaling pathway and the MAPK/ERK signaling pathway.