LncRNA MALAT1调控miR-200b-3p/HK2对鼻咽癌细胞增殖、凋亡及糖酵解的影响  

Impacts of LncRNA MALAT1 on proliferation,apoptosis and glycolysis of nasopharyngeal carcinoma cells via regulating miR-200b-3p/HK2

作　　者：林晓辉 余海清[2] 缪文强[2] 王树滨 LIN Xiaohui;YU Haiqing;MIAO Wenqiang;WANG Shubin(2023 Graduate Students,Shantou University Medical College,Shantou Guangdong 515041;Department of Oncology,Shenzhen Bao’an District People’s Hospital,Shenzhen Guangdong 518101;Department of Oncology,Peking University Shenzhen Hospital,Shenzhen Guangdong 518036,China)

机构地区：[1]汕头大学医学院,广东汕头515041 [2]深圳市宝安区人民医院肿瘤内科,广东深圳518101 [3]北京大学深圳医院肿瘤内科,广东深圳518036

出　　处：《临床与病理杂志》2023年第8期1498-1506,共9页Journal of Clinical and Pathological Research

摘　　要：目的:长链非编码RNAs(long non-coding RNAs,lncRNAs)参与多种癌症进展,但lncRNAs肺腺癌转移相关转录子1(metastasis associated lung adenocarcinoma transcript 1,MALAT1)在鼻咽癌(nasopharyngeal carcinoma,NPC)中的生物学作用尚不清楚。本研究探讨lncRNA MALAT1调控微RNA(microRNA,miR)-200b-3p/己糖激酶2(hexokinase 2,HK2)对NPC细胞增殖、侵袭、迁移及糖酵解的影响。方法:将NPC细胞系CNE-2分为对照组、小干扰(si)-阴性对照(negative control,NC)组、si-MALAT1组、si-MALAT1+抑制剂(inhibitor)-NC组、si-MALAT1+miR-200b-3p inhibitor组,real-time PCR检测各组细胞MALAT1、miR-200b-3p表达;细胞计数试剂盒8(cell counting kit 8,CCK-8)、流式细胞术、蛋白质印迹法和分光光度法分别检测细胞增殖、凋亡、HK2蛋白表达及糖代谢水平;双荧光素酶实验验证MALAT1、miR-200b-3p和HK2的关系。结果:与对照组、si-NC组比较,si-MALAT1组CNE-2细胞中miR-200b-3p表达升高、MALAT1、HK2表达降低,细胞增殖能力降低,细胞凋亡升高,葡萄糖消耗、乳酸生成均降低(均P<0.05);与si-MALAT1组、si-MALAT1+inhibitor-NC组比较,si-MALAT1+miR-200b-3p inhibitor组miR-200b-3p表达降低,MALAT1、HK2表达升高,细胞增殖能力升高、细胞凋亡降低,葡萄糖消耗、乳酸生成均升高(均P<0.05)。MALAT1与miR-200b-3p、miR-200b-3p与HK2之间存在靶向调控关系。结论:沉默表达MALAT1可能通过上调miR-200b-3p来下调HK2表达,从而抑制CNE-2细胞增殖、迁移与侵袭及其糖酵解水平,其有望成为NPC治疗的潜在靶点。Objective:Long non-coding RNAs(lncRNAs)have been reported to be involved in the progression of multiple cancers,but the biological role of lncRNA metastasis associated lung adenocarcinoma transcript 1(MALAT1)in nasopharyngeal carcinoma(NPC)is unclear.This study aims to explore the impacts of lncRNA MALAT1 on the proliferation,invasion,migration and glycolysis of NPC cells by regulating micro RNA(miR)-200b-3p/hexokinase 2(HK2).Methods:The NPC cells CNE-2 were divided into a control group,a si-negative control(NC)group,a si-MALAT1 group,a si-MALAT1+inhibitor-NC group,and a si-MALAT1+miR-200b-3p inhibitor group.Real-time PCR was used to detect the expression of MALAT1 and miR-200b-3p in each group;the cell proliferation,apoptosis,cell counting kit 8(CCK-8),flow cytometry,and Western blotting were used to assess cell proliferation,apoptosis,HK2 protein expression,and glucose metabolism,respectively.Dual-luciferase assay was performed to validate the relationship between MALAT1,miR-200b-3p and HK2.Results:In CNE-2 cells,compared to the control group and the si-NC group,the expression of miR-200b-3p was increased,the expressions of MALAT1 and HK2 were decreased,the proliferation ability was reduced,the apoptosis was increased,and the glucose and lactic acid consumption were decreased in the si-MALAT1 group(all P<0.05).Compared to the si-MALAT1 group and the si-MALAT1+inhibitor-NC group,the expression of miR-200b-3p was reduced,the expressions of MALAT1 and HK2 were increased,the proliferation ability was enhanced,the apoptosis was reduced,and the glucose and lactic acid consumption were increased in the si-MALAT1+miR-200b-3p inhibitor group(all P<0.05).There was a targeted regulatory relationship between MALAT1 and miR-200b-3p,as well as between miR-200b-3p and HK2.Conclusion:Silencing MALAT1 may potentially downregulate the expression of HK2 via upregulating miR-200b-3p,thereby inhibiting the proliferation,migration and invasion,and glycolysis levels of CNE-2 cells.This has the potential to become a target for the tre

关 键 词：长链非编码RNA 微RNA-200b-3p 己糖激酶2 鼻咽癌 增殖 

分 类 号：R739.63[医药卫生—肿瘤]