LncMALAT1通过竞争性结合miR-506-3p调控EZH2影响膀胱癌增殖的机制研究

doi:10.20223/j.cnki.1000-8535.2025.10.018

摘要/Abstract

摘要： 目的探讨长链非编码核糖核酸肺腺癌转移相关转录本 1（LncMALAT1）通过竞争性结合微小RNA-506-3p（miR-506-3p）调控Zeste同源物增强子2（EZH2）影响膀胱癌增殖的机制。方法收集2023年1月—2024年10月的92例外科手术切除的膀胱癌组织及对应的癌旁组织标本,利用Western blot和定量实时逆转录聚合酶链式反应（qRT-PCR）方法检测LncMALAT1和EZH2的表达情况。根据患者预后分为不良组（n=34）和良好组（n=58）,收集患者的性别、年龄、肿瘤直径、血管侵袭情况、TNM分期、远处转移情况等临床指标,结合临床病理指标分析LncMALAT1和EZH2与膀胱癌患者预后的关系。通过体外实验,包括qRT-PCR、Western blot、平板克隆和EdU实验,验证LncMALAT1对EZH2表达和膀胱癌细胞增殖的影响。利用生物信息学技术预测LncMALAT1与miR-506-3p的相互作用,并通过qRT-PCR验证在膀胱癌细胞中上调LncMALAT1表达后miR-506-3p的表达变化。结果单因素结果显示,血管侵袭情况、TNM分期、远处转移情况、LncMALAT1及EZH2表达水平均与膀胱癌患者预后不良有关,差异有统计学意义（均P<0.05）。分析结果发现LncMALAT1与EZH2在膀胱癌组织中的表达呈正相关。体外实验结果显示,上调LncMALAT1表达后,EZH2的表达显著上调,且膀胱癌细胞的增殖能力显著提高（均P<0.05）。qRT-PCR验证表明,上调LncMALAT1表达后,miR-506-3p的表达显著下调（P<0.05）,提示LncMALAT1通过竞争性结合miR-506-3p调控EZH2,进而影响膀胱癌细胞的增殖进展。结论 LncMALAT1通过竞争性结合miR-506-3p调控EZH2促进膀胱癌增殖功能,进而加快膀胱癌细胞的增殖进展,可为膀胱癌的治疗提供新的潜在靶点。

关键词: LncMALAT1, miR-506-3p, EZH2, 膀胱癌, 增殖

Abstract: Objective To explore the mechanism of long non-coding ribonucleic acid metastasis - associated lung adenocarcinoma transcript 1（LncMALAT1）regulating enhancer of Zeste homolog 2（EZH2）through competitive combination with microRNA-506-3p（miR-506-3p）to affect the proliferation of bladder cancer．Methods A total of 92 pairs of bladder cancer tissues and corresponding adjacent normal tissues were collected from surgical resections between January 2023 and October 2024．The expression levels of LncMALAT1 and EZH2 were detected using Western blot and qRT-PCR．The patients were divided into poor group（n=34）and good group（n=58）according to their prognosis．Clinical data,such as gender,age,tumor diameter,vascular invasion,TNM stage,and distant metastasis were collected,and the relationship between LncMALAT1 and EZH2 and the prognosis of bladder cancer patients was analyzed with clinical pathological indicators．Through in vitro experiments,including qRT-PCR Western blot,plate cloning and EdU experiment were conducted to verify the effect of LncMALAT1 on EZH2 expression and bladder cancer cell proliferation．Bioinformatics technology was used to predict the interaction between LncMALAT1 and miR-506-3p,and qRT-PCR was used to verify the change of miR-506-3p expression after up regulating LncMALAT1 expression in bladder cancer cells．Results The univariate results showed that vascular invasion,TNM stage,distant metastasis,LncMALAT1 and EZH2 expression levels were related to the poor prognosis of bladder cancer patients,and the difference was statistically significant（all P<0.05）．The results showed that the expression of LncMALAT1 and EZH2 in bladder cancer was positively correlated．In vitro experiment results showed that after up regulating LncMALAT1 expression,EZH2 expression was significantly up-regulated,and the proliferation ability of bladder cancer cells was significantly improved（all P<0.05）．QRT-PCR validation showed that the expression of miR-506-3p was significantly down regulated after the expression of LncMALAT1 was up-regulated（P<0.05）,suggesting that LncMALAT1 could regulate EZH2 through competitive combination with miR-506-3p,thereby affecting the proliferation and progression of bladder cancer cells．Conclusions LncMALAT1 can promote the proliferation of bladder cancer cells by competitively combining with miR-506-3p to regulate EZH2,and then accelerate the proliferation of bladder cancer cells,which can provide a new potential target for the treatment of bladder cancer．

Key words: LncMALAT1, miR-506-3p, EZH2, bladder cancer, proliferation

宋磊, 王乐. LncMALAT1通过竞争性结合miR-506-3p调控EZH2影响膀胱癌增殖的机制研究[J]. 广州医药, 2025, 56(10): 1440-1447.

SONG Lei, WANG Le. The mechanism of LncMALAT1 regulating EZH2 by competitively combining with miR-506-3p to affect the proliferation of bladder cancer[J]. Guangzhou Medical Journal, 2025, 56(10): 1440-1447.

参考文献

[1] 郑盛锋,朱一平,叶定伟.2022年度膀胱癌基础研究及临床诊疗新进展[J].中国癌症杂志,2023,33(3):201-209.
[2] SHEN W,YU Q,PU Y,et al.Upregulation of long noncoding RNA MALAT1 in colorectal cancer promotes radioresistance and aggressive malignance[J].Int J Gen Med,2022(15):8365-8380.
[3] ZHAO H,WANG Y,HOU W,et al.Long non-coding RNA MALAT1 promotes cell proliferation,migration and invasion by targeting miR-590-3p in osteosarcoma[J].Exp Ther Med,2022,24(5):672.
[4] 王小蕊,董非斐,何碧凝,等.miR-506-3p通过靶向IQGAP1基因抑制甲状腺癌细胞增殖、迁移和侵袭的体外研究[J].中国老年学杂志,2021,41(18):4073-4078.
[5] 陈瑜,张永珍,王永强,等.miR-506-3p通过靶向结合SART3抑制葡萄膜黑色素瘤恶性表型[J].现代肿瘤医学,2023,31(19):3557-3565.
[6] MOHAMEDALI R,MITRA S,MANDAL S,et al.Expression of EZH2 and H3K27me3 predicts tumor biology of urothelial carcinoma[J].Indian J Pathol Microbiol,2023,66(3):488-494.
[7] 中国肿瘤医院泌尿肿瘤协作组,叶定伟.膀胱癌早诊早治专家共识(2024年版)[J].中国癌症杂志,2024,34(6):607-618.
[8] 刘洪杰,许振强,苏陈强,等.基于TURBT的保留膀胱综合疗法对T2期肌层浸润性膀胱癌患者术后并发症及疾病复发的影响[J].医学理论与实践,2023,36(21):3663-3665.
[9] 谢文亮,李明.基于GEO数据库筛选非肌层浸润性膀胱癌吉西他滨耐药的免疫相关标志物[J].现代泌尿生殖肿瘤杂志,2024,16(1):49-51.
[10] HU L,XIE K,ZHENG C,et al.Exosomal MALAT1 promotes the proliferation of esophageal squamous cell carcinoma through glyoxalase 1-dependent methylglyoxal removal[J].Noncoding RNA Res,2024,9(2):330-340.
[11] 茆艳,周国平.长链非编码RNA MALAT1与肿瘤性疾病相关性的研究进展[J].现代肿瘤医学,2020,28(5):862-866.
[12] 朱骊. 组蛋白甲基化转移酶SETD2与EZH2相互作用影响鼻咽癌细胞侵袭转移的机制研究[D].贵阳:贵州医科大学,2023.
[13] 于帆,张弛,周正,等.MicroRNA在膀胱癌中作用的研究进展[J].牡丹江医学院学报,2021,42(5):138-139,146.
[14] 段斌,符浩,王昕禧.LncRNA MALAT1靶向调控miR-146b-5p影响膀胱癌细胞侵袭和迁移[J].中国病理生理杂志,2020,36(1):82-88.
[15] 罗黔,吕杰,王宁.LncRNA MALAT1/miR-30a/SOX4通路调节膀胱癌细胞增殖、侵袭和迁移[J].中国临床解剖学杂志,2020,38(3):295-300.
[16] 孔钰琳,荣胜忠,王慧单,等.不同基因作为竞争性内源RNA参与膀胱癌调控的研究进展[J].现代肿瘤医学,2021,29(20):3662-3668.
[17] 田虹,陈颖,唐力,等.膀胱癌ceRNA网络的构建和相关lncRNAs的筛选[J].中国科技论文在线精品论文,2024,17(2):213-223.
[18] 吴娟,王丹,张前进,等.膀胱癌100例血清Zeste基因增强子同源物2和信号传导蛋白3表达水平及诊断价值分析[J].安徽医药,2024,28(10):2035-2038.
[19] 陈翔,何天基,冉俊武,等.EZH2抑制剂对膀胱癌T24细胞上皮间质转化的影响及其机制研究[J].中国现代医学杂志,2022,32(8):39-45.