LncRNA-HAGLROS调控miR-26b/JAK2/STAT3通路对肝癌细胞上皮间质转化的影响  

The Effect of LncRNA Haglros Regulating miR-26b/JAK2/STAT3 Pathway on Epithelial Mesenchymal Transition of Hepatocellular Carcinoma Cells

作　　者：李肖芸 方家远 闫春雷 宋华勇[1] LI Xiaoyun;FANG Jiayuan;YAN Chunlei(The First Affiliated Hospital of Henan University,Kaifeng,475000)

机构地区：[1]河南大学第一附属医院,475000

出　　处：《实用癌症杂志》2024年第2期175-180,共6页The Practical Journal of Cancer

基　　金：河南省医学科技攻关计划项目(编号:LHGJ20200539)。

摘　　要：目的探讨长链非编码RNA(long non-coding RNA,LncRNA)HAGLR互补链LncRNA(HAGLROS)调控微小RNA((miRNA,miR)-26b/非受体型酪氨酸蛋白激酶(janus kinase 2,JAK2)/信号传导和转录激活因子3(signal transducer and activator of transcription3,STAT3)通路对肝癌细胞上皮间质转化的影响。方法获取正常肝细胞系及肝癌细胞系,依据转染情况分组,即si-NC组、si-HAGLROS组、miR-26 inhibitor组、si-HAGLROS+miR-26 inhibitor组。MTT实验检测各组细胞增殖活性,细胞划痕实验检测各组细胞迁移情况,细胞侵袭实验检测各组细胞侵袭能力,qPCR法检测HAGLROS、miR-26b、上皮钙粘蛋白(E-cadherin,E-cad)、N-钙黏素(N-cadherin)、纤维粘连蛋白(fibronectin,FN)、抗凋亡蛋白(Bcl-2)表达,双荧光素酶报告基因实验验证LncRNA-HAGLROS与miR-26b的靶向关系。结果肝癌细胞系Hep3B、MHCC-LM3、Huh7、SMMC-7721中HAGLROS表达均显著高于LO2细胞(P<0.05),miR-26b表达与之相反。生物信息学软件显示,HAGLROS可与miR-26b靶向结合。肝癌细胞功能实验显示,与si-NC组比较,si-HAGLROS组细胞增殖活性、细胞划痕愈合率、细胞穿膜数目、N-cadherin、FN、Bcl-2、p-JAK2、p-STAT3表达均更低,E-Cadherin表达更高;而miR-26b inhibitor组细胞增殖活性、细胞划痕愈合率、细胞穿膜数目、N-cadherin、FN、Bcl-2、p-JAK2、p-STAT3表达均更高,E-Cadherin表达更低;si-NC组与si-HAGLROS+miR-26b inhibitor组比较,差异均无统计学意义(P>0.05)。结论LncRNA-HAGLROS可通过靶向下调miR-26b促进肝癌细胞生物行为,如迁移、侵袭及EMT过程,同时可调控JAK2/STAT3通路活性,LncRNA-HAGLROS可作为肝癌治疗靶点。Objective To explore the regulation of Long non-coding RNA(LncRNA)HAGLR complementary chain LncRNA(HAGLROS)on microrNA(miRNA,miR)-26b/non-receptor protein tyrosine Kinase 2,Effect of JAK2/signal transducer and activator of transcription3(STAT3)pathway on epithelial mesenchymal transformation of hepatoma cells.Methods Normal liver cell lines and liver cancer cell lines were obtained and divided into si-NC group,si-HAGLROS group,miR-26 inhibitor group and si-HAGLROS+miR-26 inhibitor group according to transfection conditions.Cell proliferation activity was detected by MTT assay,cell migration was detected by cell scratch assay,cell invasion assay was detected by cell invasion assay,and HAGLROS,miR-26b,E-Cadherin(E-cad)and N-cadherin(N-cadherin)were detected by qPCR.E-cad),Fibronectin(FN),anti-apoptotic protein(Bcl-2)expression,dual luciferase reporter gene assay verified the targeting relationship between LncRNA-HAGLROS and miR-26b.Results The expression of HAGLROS in Hep3B,MHCC-LM3,Huh7 and SMMC-7721 cells was significantly higher than that in LO2 cells(P<0.05),while the expression of miR-26b was the opposite.The bioinformatics software showed that HAGLROS could target miR-26b.Liver cancer cell function experiment showed that compared with si-NC group,cell proliferation activity,cell scratch healing rate,cell membrane crossing number,N-cadherin,FN,Bcl-2,p-JAK2,p-STAT3 expression were lower in si-HAGLROS group,while E-Cadherin expression was higher.However,in miR-26b inhibitor group,cell proliferation activity,cell scratch healing rate,cell membrane crossing number,N-cadherin,FN,Bcl-2,p-JAK2,p-STAT3 expression were higher,while E-Cadherin expression was lower.There was no statistical significance between si-NC group and si-HAGLROS+miR-26b inhibitor group(P>0.05).Conclusion LncRNA-HAGLROS can promote the biological behavior of liver cancer cells,such as migration,invasion and EMT process,by targeting down-regulation of miR-26b,and can regulate the activity of JAK2/STAT3 pathway.LncRNA-HAGLROS can be used as a therap

关 键 词：肝癌 LncRNA-HAGLROS miR-26b JAK2/STAT3通路 上皮间质转化 分子机制 

分 类 号：R735.7[医药卫生—肿瘤]