lncRNA PSMA3-AS1调节miR-142-3p/HMGA2轴对卵巢癌恶性进展的影响  

The impacts of lncRNA PSMA3-AS1 on malignant progression of ovarian cancer by regulating miR-142-3p/HMGA2 axis

作　　者：萨日胡 赵得雄[1] 孙文萍[1] SA Rihu;ZHAO Dexiong;SUN Wenping(The Second Department of Obstetrics,Qinghai Red Cross Hospital,Qinghai Xining 810000,China)

机构地区：[1]青海红十字医院产二科,青海西宁810000

出　　处：《现代肿瘤医学》2024年第8期1401-1409,共9页Journal of Modern Oncology

基　　金：青海省卫健委医药卫生指导性课题(编号:2019-wjzdx-69)。

摘　　要：目的:探讨lncRNA PSMA3-AS1通过调节miR-142-3p/HMGA2轴对卵巢癌恶性进展的影响及其机制。方法:选择2019年3月至2022年7月期间在本院确诊的53例卵巢癌患者作为研究对象,收集患者卵巢癌组织及癌旁组织。体外培养人正常卵巢细胞HOSEpiC和卵巢癌细胞系SKOV3、OVCAR3、A2780、COV362,RT-qPCR检测卵巢癌细胞中lncRNA PSMA3-AS1表达,筛选最佳干预细胞系。双荧光素酶报告基因实验验证lncRNA PSMA3-AS1、HMGA2与miR-142-3p的靶向关系;将SKOV3细胞分为si-NC组、si-PSMA3-AS1组、si-PSMA3-AS1+anti-miR-NC组、si-PSMA3-AS1+anti-miR-142-3p组、miR-NC组、miR-142-3p mimics组、miR-142-3p mimics+pcDNA组、miR-142-3p mimics+HMGA2组,检测细胞增殖、凋亡、迁移、侵袭;Western blot检测Ki67、Cyclin D1、Bcl-2、cleaved caspase 3、HMGA2蛋白表达;小鼠移植瘤实验验证lncRNA PSMA3-AS1对卵巢癌肿瘤生长的影响。结果:与癌旁组织比较,卵巢癌组织中lncRNA PSMA3-AS1和HMGA2表达升高,miR-142-3p表达降低(P<0.05);lncRNA PSMA3-AS1和HMGA2在SKOV3细胞中表达水平最高,miR-142-3p在SKOV3细胞中表达水平最低;下拉实验和双荧光素酶报告显示,lncRNA PSMA3-AS1、HMGA2与miR-142-3p存在靶向关系;敲低lncRNA PSMA3-AS1或过表达miR-142-3p后,细胞OD值、细胞克隆数、划痕愈合率、细胞侵袭数及Ki67、Cyclin D1、Bcl-2、HMGA2表达显著降低,细胞凋亡率、cleaved caspase 3表达显著增加(P<0.05);抑制miR-142-3p表达或过表达HMGA2可逆转敲低lncRNA PSMA3-AS1或过表达miR-142-3p对卵巢癌细胞恶性行为的抑制作用;体内实验表明,敲低lncRNA PSMA3-AS1表达可抑制小鼠肿瘤生长。结论:lncRNA PSMA3-AS1在卵巢癌中高表达,敲低lncRNA PSMA3-AS1可调节miR-142-3p/HMGA2轴抑制卵巢癌恶性发展。Objective:To investigate the impacts and mechanism of lncRNA PSMA3-AS1 on malignant progression of ovarian cancer by regulating the miR-142-3p/HMGA2 axis.Methods:53 patients with ovarian cancer diagnosed in our hospital between March 2019 and July 2022 were selected for the study,and the patients'ovarian cancer tissues and paracancerous tissues were collected.Human normal ovarian cells HOSEpiC and ovarian cancer cell lines SKOV3,OVCAR3,A2780,COV362 were cultured in vitro.RT-qPCR was applied to detect the expression of lncRNA PSMA3-AS1 in ovarian cancer cells to screen the optimal intervention cell line.The double luciferase reporter gene experiment was applied to verify the targeting relationship between lncRNA PSMA3-AS1,HMGA2 and miR-142-3p.SKOV3 cells were separated into si-NC group,si-PSMA3-AS1 group,si-PSMA3-AS1+anti-miR-NC group,si-PSMA3-AS1+anti-miR-142-3p group,miR-NC group,miR-142-3p mimics group,miR-142-3p mimics+pcDNA group,and miR-142-3p mimics+HMGA2 group.Cell proliferation,apoptosis,migration,and invasion were detected.Western blot was applied to detect the expression of Ki67,Cyclin D1,Bcl-2,cleaved caspase 3,and HMGA2 proteins.The mouse transplantation tumor experiment was applied to verify the effect of lncRNA PSMA3-AS1 on the growth of ovarian cancer tumors.Results:Compared with paracancerous tissue,lncRNA PSMA3-AS1 and HMGA2 expression was elevated and miR-142-3p expression was decreased in ovarian cancer tissue(P<0.05).lncRNA PSMA3-AS1 and HMGA2 had the highest expression in SKOV3 cells,and miR-142-3p had the lowest expression level in SKOV3 cells.Pull down test and double luciferase report showed that lncRNA PSMA3-AS1,HMGA2 had a targeting relationship with miR-142-3p.After knocking down lncRNA PSMA3-AS1 or overexpressing miR-142-3p,the cell OD,cell clone number,scratch healing rate,cell invasion number,and the expression of Ki67,Cyclin D1,Bcl-2,HMGA2 were obviously reduced,while cell apoptosis rate and the expression of cleaved caspase 3 were obviously increased(P<0.05).Inhibiting the expressi

关 键 词：lncRNA PSMA3-AS1 miR-142-3p/HMGA2 细胞增殖 细胞迁移 细胞侵袭 

分 类 号：R737.31[医药卫生—肿瘤]