PTENp1作为miR-21吸附“海绵”在口腔鳞癌中调控PTEN的表达  

Expression of PTEN regulated by PTENp1 as a “sponge”adsorbed by miR-21 in oral squamous cell carcinoma

作　　者：张琳梅 陈诚[2] 张耀超 高岭[3] 李少明[3] ZHANG Linmei;CHEN Cheng;ZHANG Yaochao;GAO Ling;LI Shaoming(Stomatology Department of Xi'an Medical College,Xi'an 710021;Department of General Dentistry,Xi'an Jiaotong University Stomatological Hospital,Xi'an 710004;Department of Maxillofacial Surgery,The Affiliated Hospital of Qingdao University,Qingdao 266555,China)

机构地区：[1]西安医学院口腔医学院,陕西西安710021 [2]陕西省颅颌面精准医学研究重点实验室,西安交通大学口腔医院口腔综合科,陕西西安710004 [3]青岛大学附属医院口腔颌面外科,山东青岛266555

出　　处：《西安交通大学学报（医学版）》2020年第5期713-717,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金面上项目(No.81472520);陕西省教委基金资助项目(No.19JK0764)。

摘　　要：目的阐述肿瘤抑制因子假基因(PTENp1)在口腔鳞状细胞癌(oral squamous cell carcinoma,OSCC)中调控PTEN mRNA表达的作用,从而为OSCC的预防、治疗及预后提供新靶点。方法收集42例OSCC患者以及癌旁正常组织标本,提取RNA,通过qRT-PCR技术检测PTENp1、PTEN以及miR-21的表达,Pearson相关分析其相关性。培养HEK293细胞并分组分别转染PTEN的3′UTR的荧光素酶质粒和miR-21模拟剂(mimics)或抑制剂(inhibitor)或者全长PTENp13′UTR质粒,通过荧光素酶活性检测验证PTENp1在PTEN-miR-21轴中的调节作用以及促癌功能。结果qRT-PCR检测发现,OSCC组织标本中PTEN(85.7%)、PTENp1(90.4%)均呈现缺失,而miR-21(76.2%)呈高表达趋势。Pearson相关性分析发现,PTEN与miR-21表达呈负相关(R=-0.1235,P<0.001),而PTEN与PTENp1表达存在正相关(R=0.0518,P=0.01)。荧光素酶活性检测显示,高表达PTENp1可显著上调PTEN的表达,提示PTENp1可靶向竞争性结合miR-21调节PTEN的表达。结论PTENp1作为PTEN的内源竞争性RNA(ceRNA)竞争性结合miR-21,对于OSCC的早期标记物预测及靶向治疗提供新的思路。Objective To explore the role of the new regulator pseudogene phosphatase and tensin homolog pseudogene 1(PTENp1)in the regulation of PTEN mRNA and gene expression in oral squamous cell carcinoma(OSCC)so as to provide a new target for the prevention,treatment and outcome of OSCC.Methods First,we collected 42 specimens of OSCC and normal tissues,extracted RNA,detected the expressions of PTENp1,PTEN and miR-21 by qRT-PCR,and studied their correlation by Pearson correlation analysis.HEK293 cells were cultured and transfected with luciferase plasmid of 3 UTR of PTEN and mimic or inhibitor of miR-21 or full-length PTENp13 UTR plasmid,respectively.The regulatory role of PTENp1 in PTEN-miR-21 axis and its cancer promoting function were verified by luciferase activity test.Results qRT-PCR showed that the expressions of PTEN(85.7%)and PTENp1(90.4%)were significantly repressed in the OSCC tissues while miR-21 expression(76.2%)was remarkably increased.Pearson correlation analysis showed that PTEN expression was negatively correlated with miR-21 expression ( R =0.123 5, P <0.001) but positively correlated with PTENp1 expression ( R = 0.051 8 , P = 0.01 ). The results of luciferase activity showed that PTEN expression was significantly up-regulated by overexpression of PTENp1, suggesting that PTENp1 could target competitive binding miR-21 to regulate PTEN expression. Conclusion PTENp1, as the ceRNA of PTEN, competitively binds the miR-21, which provides a new idea for predicting the early marker and targeting therapy of OSCC in the future.

关 键 词：口腔鳞状细胞癌 肿瘤抑制因子假基因(PTENp1) 人第10号染色体缺失的磷酸酶及张力蛋白同源基因(PTEN) MIR-21 内源竞争性RNA 

分 类 号：R739.81[医药卫生—肿瘤]