miR-2110通过调节CDT1影响肺腺癌的生物学行为  

miR-2110 Affects the Biological Behaviors of Lung Adenocarcinoma by Regulating CDT1

作　　者：米源[1] 李旭哲 王聪 蔺晨曦 赵志超 颜晓菲 史平 王雷[4] MI Yuan;LI Xuzhe;WANG Cong;LIN Chenxi;ZHAO Zhichao;YAN Xiaofei;SHI Ping;WANG Lei(Department of Emergency,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050017,China;Department of Clinical Medicine,School of Basic Medicine,Hebei Medical University,Shijiazhuang 050017,China;College of Pharmacy,Hebei Medical University,Shijiazhuang 050017,China;Department of Thoracic Surgery,The Fourth Hospital of Hebei Medical University,Shijiazhuang 050017,China;Department of Neurology,Yongqing County People's Hospital,Langfang 065600,China;Outpatient Department,Shijiazhuang Fifth Retired Cadre Nursing Home of Hebei Military Area Command,Shijiazhuang 050011,China;Outpatient Department,Baoding Second Retired Cadre Nursing Home of Hebei Military Area Command,Baoding 071000,China)

机构地区：[1]河北医科大学第四医院急诊科,石家庄050017 [2]河北医科大学基础医学院临床医学系,石家庄050017 [3]河北医科大学药学院,石家庄050017 [4]河北医科大学第四医院胸二科,石家庄050017 [5]永清县人民医院神经内科,廊坊065600 [6]河北省军区石家庄第五离职干部休养所门诊部,石家庄050011 [7]河北省军区保定第二离职干部休养所门诊部,保定071000

出　　处：《四川大学学报（医学版）》2024年第5期1202-1209,共8页Journal of Sichuan University(Medical Sciences)

基　　金：河北省卫生厅课题(No.20221353);河北省科技厅(No.22377769D);河北省省级科技计划基础研究专项(自然科学基金)联合基金项目(No.H202206391);河北医科大学第四医院科研创新团队项目(No.2023B02)资助。

摘　　要：目的通过细胞实验和动物实验结果,探讨miR-2110对肺腺癌(lung adenocarcinoma,LUAD)细胞增殖、凋亡及转移等生物学行为的影响。方法通过生物信息学网站(ENCORI、TargetScan、miRTarBase和Tarbase)分析在LUAD组织中miR-2110的表达变化并进行miR-2110靶基因的预测。收集LUAD组织样本及肺腺癌细胞通过PCR技术验证miR-2110的表达变化。采用CCK-8、克隆形成实验、Transwell和流式细胞术分析LUAD细胞的功能变化。将10只6~8周龄BALB/c雌性裸鼠随机分为2组,通过体内实验验证miR-2110对LUAD的影响。结果miR-2110在LUAD组织及细胞中相比于正常肺组织显著降低,其过表达可抑制LUAD细胞的增殖、转移并促进了肿瘤细胞的凋亡(P<0.05)。通过生物信息学预测和双荧光素酶报告基因测定,验证了miR-2110可靶向结合CDT1,并通过过表达CDT1基因发现相比于过表达miR-2110组,逆转了其增殖、转移和凋亡的作用(P<0.05)。裸鼠体内实验发现相比于对照组,过表达miR-2110可以明显降低肿瘤的增殖指标Ki67和转移指标vimentin、MMP9的表达。结论miR-2110可以通过靶向CDT1抑制LUAD的增殖、转移,为LUAD的治疗提供新的依据。Objective To investigate the effect of miR-2110 on the biological behaviors,such as cell proliferation,apoptosis,and metastasis,of lung adenocarcinoma(LUAD)cells by means of cell and animal experiments.Methods Bioinformatics websites,including ENCORI,TargetScan,miRTarBase,and Tarbase,were used to analyze the changes in the expression of miR-2110 in LUAD samples and to predict miR-2110 target.LUAD tissue samples and cells were collected and the changes in the expression of miR-2110 were verified through PCR technology.CCK-8 assay,clonogenic assay,Transwell assay,and flow cytometry were conducted to analyze alterations in the functions of LUAD cells.In addition,10 BALB/c female nude mice aged 6 to 8 weeks were randomly divided into 2 groups,and the effect of miR-2110 on LUAD was investigated by in vivo experiments.Results miR-2110 was significantly decreased in LUAD tissues and cells compared with the normal lung tissues.miR-2110 overexpression inhibited the proliferation and metastasis of LUAD cells and promoted the apoptosis of tumor cells(P<0.05).Bioinformatics prediction and dual luciferase reporter gene assay results confirmed that miR-2110 could target and bind to CDT1.In addition,overexpression of CDT1 gene reversed the proliferation,metastasis,and apoptosis of miR-2110 compared with the miR-2110 overexpression group(P<0.05).Nude mice in vivo experiments showed that miR-2110 overexpression significantly decreased the expression of Ki67,a tumor proliferation index,and vimentin and MMP9,two metastasis indices,compared with the control group.Conclusion miR-2110 can inhibit proliferation and metastasis of LUAD by targeting CDT1,providing a new rationale for the treatment of LUAD.

关 键 词：肺腺癌 miR-2110 CDT1 肿瘤增殖 

分 类 号：R734.2[医药卫生—肿瘤]