外泌体携带的miR-142-3p通过靶向COX-2抑制骨肉瘤细胞的增殖和侵袭  

The miR-142-3p carried by exosomes inhibits the proliferation and invasion of osteosarcoma cells by targeting COX-2

作　　者：张金山 鲁厚根[1] 刘伟 孙晓峰 ZHANG Jinshan;LU Hougen;LIU Wei;SUN Xiaofeng(Department of Orthopedics,the Second Clinical Hospital of Yangtze University/Jingzhou Central Hospital,Hubei Jingzhou 434000,China;Department of Orthopedics,the Third Affiliated Hospital of Chongqing Medical University,Chongqing 401120,China;School of Basic Medicine,Chongqing Medical University,Chongqing 400016,China)

机构地区：[1]长江大学第二临床医学院/荆州市中心医院骨科,湖北荆州434000 [2]重庆医科大学附属第三医院骨科,重庆401120 [3]重庆医科大学基础医学院,重庆400016

出　　处：《现代肿瘤医学》2021年第15期2575-2581,共7页Journal of Modern Oncology

基　　金：重庆市技术创新与应用发展专项面上项目(编号:cstc2019jscx-msxmX0853)。

摘　　要：目的:探讨骨肉瘤组织中miR-142-3p是否可以通过靶向COX-2来抑制肿瘤细胞增殖和侵袭能力,并且验证携带miR-142-3p的外泌体是否可以抑制骨肉瘤细胞生长。方法:检测骨肉瘤癌组织及癌旁组织中miR-142-3p和COX-2 mRNA的表达。用双荧光素酶报告基因实验验证miR-142-3p与COX-23'UTR的靶向关系。构建过表达miR-142-3p及COX-2细胞系,检测细胞的增殖及侵袭能力。用携带miR-142-3p的外泌体处理肿瘤细胞,检测细胞的增殖及侵袭能力。对携带miR-142-3p的外泌体进行体内抑瘤实验。结果:较癌旁组织而言,miR-142-3p在癌组织中显著低表达(P<0.05),而COX-2在癌组织中显著高表达(P<0.05),且COX-2是miR-142-3p的靶标。过表达miR-142-3p的细胞增殖及侵袭能力降低(P<0.001)。体外增殖实验及小鼠体内移植瘤模型表明,携带miR-142-3p的外泌体可以在小鼠体内外抑制骨肉瘤细胞的增殖(P<0.001)。结论:携带miR-142-3p的外泌体可通过抑制COX-2的表达来抑制骨肉瘤细胞的生长,因此,携带miR-142-3p的外泌体可能发展成为一种治疗骨肉瘤的潜在策略。Objective:To investigate whether miR-142-3p could inhibit the proliferation and invasion of osteosarcoma cells by targeting COX-2 and to verify whether exosomes carrying miR-142-3p could inhibit the growth of osteosarcoma cells.Methods:The expression of miR-142-3p and COX-2 mRNA in osteosarcoma and adjacent tissues was detected.The interaction relationship between miR-142-3p and COX-23'UTR was verified by luciferase reporter assay.Overexpressing miR-142-3p and COX-2 cell lines were constructed,and the proliferation and invasion ability of the cells were detected.Tumor cells were co-cultured with exosome carrying miR-142-3p,and the proliferation and invasion ability of tumor cells were detected.The anti-tumor experiment in vivo was observed by the administration of exosome carrying the miR-142-3p to mice.Results:Compared with adjacent tissues,the expression of miR-142-3p was significantly lower in cancer tissues(P<0.05),while the expression of COX-2 in cancer tissues was significantly higher(P<0.05)and COX-2 was the target of miR-142-3p.The results showed that the proliferation and invasion ability of cells transfected with miR-142-3p mimics were reduced(P<0.001).The experiment of proliferation in vitro and the transplanted tumor model in vivo showed that the exosome carrying miR-142-3p could inhibit the proliferation of osteosarcoma cells(P<0.001).Conclusion:Exosomes carrying miR-142-3p can inhibit the growth of osteosarcoma cells by inhibiting the expression of COX-2.Therefore,exosomes carrying miR-142-3p may develop into a potential strategy for osteosarcoma.

关 键 词：骨肉瘤 miR-142-3p COX-2 外泌体 

分 类 号：R738[医药卫生—肿瘤]