circFTO靶向JAK2/STAT3信号通路促进鼻咽癌的恶性进展

circFTO promotes malignant progression of nasopharyngeal carcinoma by targeting the JAK2/STAT3 signaling pathway

目的:探讨circFTO在鼻咽癌(nasopharyngeal carcinoma,NPC)组织中的表达及其调控鼻咽癌恶性进展的机制。方法:使用荧光原位杂交技术(fluorescence in situ hybridization,FISH)检测鼻咽癌癌组织和癌旁组织中circFTO的表达水平及circFTO亚细胞定位。采用RT-qPCR检测鼻咽癌细胞系中的circFTO表达水平。同时构建circFTO干扰载体转染鼻咽癌细胞,并利用流式细胞术、EDU实验、CCK-8、Western blot等探索circFTO在鼻咽癌中的功能。结果:circFTO在鼻咽癌组织和细胞中表达上调,且circFTO主要定位在细胞质中(P<0.01)。沉默circFTO能显著抑制鼻咽癌细胞的增殖、迁移能力,促进鼻咽癌细胞的凋亡和凋亡相关蛋白的表达(P<0.05)。沉默circFTO会将鼻咽癌细胞的细胞周期阻遏于G_(0)/G_(1)期(P<0.0001)。此外,机制研究表明,沉默circFTO会显著下调鼻咽癌细胞中pJAK2和pSTAT3蛋白的表达,同时抑制上皮间充质转化(epithelial-mesenchymal transition,EMT)(P<0.05)。结论:circFTO在鼻咽癌组织和细胞中高表达,并可能通过靶向JAK2/STAT3信号通路来调节上皮间充质转化最终影响鼻咽癌的恶性进展。

Objective:To investigate the expression of circFTO in nasopharyngeal carcinoma(NPC)and its mechanism of regulating the malignant progression of nasopharyngeal carcinoma.Methods:The expression of circFTO and subcellular localization of circFTO in nasopharyngeal carcinoma cancer tissues and paracancer tissues were detected by fluorescence in situ hybridization(FISH).The expression of circFTO in nasopharyngeal carcinoma cell lines was identified using RT-qPCR.At the same time,circFTO interference vector was constructed to transfect nasopharyngeal carcinoma cells.Flow cytometry,EDU assay,CCK-8 and Western blot were used to explore the function of circFTO in nasopharyngeal carcinoma.Results:circFTO expression was upregulated in nasopharyngeal carcinoma and circFTO was mainly localized in the cytoplasm(P<0.05).Down-regulation of circFTO significantly inhibited the proliferation and migration of nasopharyngeal carcinoma cells,and increased apoptosis and apoptosis-related protein expression of nasopharyngeal carcinoma cells(P<0.05).Silencing circFTO inhibited the cell cycle of nasopharyngeal carcinoma cells in the G_(0)/G_(1) phase(P<0.0001).In addition,mechanism studies had shown that circFTO silencing can significantly down-regulate the expression of pJAK2 and pSTAT3 in nasopharyngeal carcinoma cells,and inhibit the epithelial-mesenchymal transition(EMT)(P<0.05).Conclusion:circFTO is highly expressed in nasopharyngeal carcinoma tissues and nasopharyngeal carcinoma cells,and may regulate epithelial-mesenchymal transformation to regulate malignant progression of nasopharyngeal carcinoma by regulating JAK2/STAT3 signaling pathway.