长链非编码RNA MSC-AS1通过调控miR-302c-3p/SSX2IP促进非小细胞肺癌细胞增殖  

Long noncoding RNA MSC-AS1 promoted cell proliferation of non-small cell lung cancer by regulating miR-302c-3p/SSX2IP

作　　者：李永超[1] 张天择 雷加吉[1] 徐广全[1] LI Yongchao;ZHANG Tianze;LEI Jiaji;XU Guangquan(Department of Thoracic Surgery,Second Affiliated Hospital of Harbin Medical University,Heilongjiang Harbin 150086,China)

机构地区：[1]哈尔滨医科大学附属第二医院胸外科二病房,黑龙江哈尔滨150086

出　　处：《现代肿瘤医学》2021年第17期2945-2951,共7页Journal of Modern Oncology

基　　金：黑龙江省卫生委科研课题(编号:2018506)。

摘　　要：目的:检测长链非编码RNA肌蛋白反义RNA1(musculin antisense RNA 1,MSC-AS1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)组织和细胞中的表达,研究其对肿瘤细胞增殖的影响并探索其机制。方法:采用qRT-PCR技术检测NSCLC肿瘤组织、癌旁组织、肺癌细胞及正常肺上皮细胞中MSC-AS1的表达;分析患者的临床病理资料与MSC-AS1表达的相关性。利用Lipofectamine TM 2000对肺癌细胞进行转染;MTT及克隆形成实验测定细胞的增殖能力;同时利用qRT-PCR测定细胞中miR-302c-3p及SSX2IP的表达变化。生物信息学方法预测MSC-AS1及miR-302c-3p的下游靶基因;双荧光素酶报告实验验证基因间的靶向结合关系。结果:MSC-AS1在肺癌组织及肺癌细胞(A549、SPC-A1和SK-MES-1)中较癌旁组织及正常肺上皮细胞BEAS-2B中表达升高(P<0.05);MSC-AS1的表达水平与癌肿TNM分期、肿瘤大小及淋巴结转移密切相关(P<0.01),并提示患者的预后不良(P<0.01);敲低MSC-AS1能够抑制肿瘤细胞的增殖(P<0.05)。MSC-AS1通过miR-302c-3p/SSX2IP轴调控NSCLC细胞的增殖。结论:LncRNA MSC-AS1能够促进NSCLC细胞的增殖并可能成为潜在的治疗靶点。Objective:To detect the expression of lncRNA MSC-AS1 in NSCLC tissues and cells and investigate its roles on tumor cells proliferation,and explore the underlying mechanism.Methods:The relative expression of MSC-AS1 in NSCLC tissues,adjacent tissues,lung cancer cells and normal pulmonary epithelial cells was determined by qRT-PCR,and the association between MSC-AS1 expression and clinicopathologic data of patients was analyzed.Lipofectamine TM 2000 was used for transfection in NSCLC cells.MTT assay and clone formation assay were performed to measure the NSCLC cells proliferation.Meanwhile,the expression of miR-302c-3p and SSX2IP was determined by qRT-PCR.Bioinformatics methods were used to predict the downstream target genes of MSC-AS1 and miR-302c-3p.The double luciferase reporter assay was performed to validate the targeted binding relationship between genes.Results:LncRNA MSC-AS1 was abnormally upregulated in NSCLC tissues and cell lines(A549,SPC-A1 and SK-MES-1)compared with adjacent tissues and normal pulmonary epithelial cells BEAS-2B(P<0.05).The high expression of MSC-AS1 was correlated with TNM stage,tumor size and lymph node metastasis(P<0.01),and indicated poor prognosis of NSCLC patients(P<0.01).Knockdown of MSC-AS1 could inhibit NSCLC cells proliferation(P<0.05).In mechanism,MSC-AS1 could regulate NSCLC cells proliferation by regulating miR-302c-3p/SSX2IP pathway.Conclusion:The data demonstrated that lncRNA MSC-AS1 could promote tumor proliferation and might be the potential therapeutic target for NSCLC treatment.

关 键 词：非小细胞肺癌 长链非编码RNA MSC-AS1 miR-302c-3p SSX2IP 

分 类 号：R734.2[医药卫生—肿瘤]