长链非编码RNA-02075参与调节子宫内膜异位症内膜基质细胞糖酵解的实验研究  

Effect of Long Non-Coding RNA-02075 on Glycolysis in Endometrium Stromal Cells of Endometriosis:A Preliminary Experimental Study

作　　者：朱佩佩 李凯全 钟晨怡 舒黎[1] 吴春香[1] 刘金勇[1] 侯振[1] 刁飞扬[1] 冒韵东[1] ZHU Pei-pei;LI Kai-quan;ZHONG Chen-yi;SHU Li;WU Chun-xiang;LIU Jin-yong;HOU Zhen;DIAO Fei-yang;MAO Yun-dong(Reproductive Medicine Center,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Affiliated Suzhou Hospital of Nanjing Medical University,Suzhou 215002,Jiangsu Province,China)

机构地区：[1]南京医科大学第一附属医院生殖医学中心,210029 [2]南京医科大学附属苏州医院

出　　处：《国际生殖健康／计划生育杂志》2023年第4期265-271,共7页Journal of International Reproductive Health/Family Planning

基　　金：国家自然科学基金(81671438);国家重点研发计划(2017YFC1001604)。

摘　　要：目的:比较子宫内膜异位症(endometriosis,EMs)患者在位和异位内膜中长链非编码RNA-02075(LINC02075)的表达水平,研究LINC02075对内膜基质细胞糖酵解的调节作用。方法:收集10例23~36岁EMs患者的在位和异位内膜,以及10例25~36岁接受宫内节育器(intrauterine device,IUD)置入手术的健康女性的子宫内膜,采用实时荧光定量聚合酶链反应(polymerase chain reaction,PCR)检测LINC02075的表达;培养异位内膜基质细胞,对其进行过表达LINC02075处理,以空白组作为对照,检测糖酵解相关酶的表达及细胞增殖、迁移和凋亡率。结果:LINC02075在内膜细胞的细胞核和细胞质中广泛表达。与正常内膜和EMs患者在位内膜比较,EMs患者异位内膜LINC02075的mRNA表达水平显著升高(P<0.05)。在异位内膜基质细胞中过表达LINC02075导致其葡萄糖的消耗显著增加(P<0.05),乳酸生成量差异无统计学意义(P>0.05),同时与糖酵解相关的酶如己糖激酶1(hexokinase 1,HK1)、丙酮酸脱氢酶激酶1(pyruvate dehydrogenase kinase 1,PDK1)、乳酸脱氢酶A(lactate dehydrogenase A,LDHA)、葡萄糖转运蛋白1(glucose transporter type 1,GLUT1)和醛缩酶A(aldolase A,ALDOA)的mRNA表达水平均呈上升趋势,其中LDHA mRNA表达水平升高,差异有统计学意义(P<0.05);异位内膜基质细胞的增殖和凋亡率均增加、迁移力降低(均P<0.05)。结论:EMs患者异位内膜中LINC02075的过表达可能通过增强糖酵解机制使异位内膜细胞增殖、迁移能力降低。Objective:To compare the expression levels of long non-coding RNA-02075(LINC02075)in the eutopic and ectopic endometrium from patients with endometriosis,and to investigate the possible roles of LINC02075 in the regulation of glycolysis in endometrial stromal cells.Methods:The samples of eutopic and ectopic endometrium were from 10 patients with endometriosis aged 23-36 years.The endometrium samples from 10 normal women accepting the surgery of intrauterine device placement aged 25-36 years were used as the control.The expression of LINC02075 was evaluated by RT-qPCR.The ectopic endometrial stromal cells were in vitro cultured.The overexpression of LINC02075 was induced by the lentivirus and adenovirus vectors.The glycolytic enzymes,cell proliferation,migration and apoptosis rates were tested.Results:LINC02075 was widely expressed in the nucleus and cytoplasm of endometrial stromal cells.The expression level of LINC02075 mRNA in ectopic endometrium(the endometriosis group)was significantly higher than that in normal endometrium(the control group)and eutopic endometrium(the endometriosis group)(all P<0.05).Overexpression of LINC02075 significantly increased glucose consumption(P<0.05),and increased lactate production(but P>0.05)in ectopic endothelial stromal cells,while the expression levels of glycolysis-related enzymes such as hexokinase 1(HK1),pyruvate dehydrogenase kinase 1(PDK1),lactate dehydrogenase A(LDHA),glucose transporter type 1(GLUT1)and aldolase A(ALDOA)were also increased,among which the increased expression level of LDHA mRNA was statistically significant(P<0.05).Overexpressed LINC02075 also increased the proliferation and apoptosis and decreased the migration of endometrial stromal cells(all P<0.05).Conclusions:The abnormally elevated LINC02075 in ectopic endometrium of patients with endometriosis may promote proliferation and reduce migration of endometrial stromal cells by the enhanced glycolytic mechanism.

关 键 词：子宫内膜异位症 细胞增殖 瓦尔堡效应 肿瘤学 有氧糖酵解 LINC02075 细胞迁移 

分 类 号：R711.71[医药卫生—妇产科学]