联合靶向阻断miR-29b/92b/106b抑制胃癌细胞生长及迁移  

Combined targeting blockage of miR-29b/92b/106b inhibits gastric cancer cell growth and migration

作　　者：施莉[1] 胡丽瑜 钟定福 郭存果 施小英 SHI Li;HU Li-yu;ZHONG Ding-fu;GUO Cun-guo;SHI Xiao-ying(Department of Gastroenterology,Jinhua People’s Hospital,Jinhua 321000,China)

机构地区：[1]金华市人民医院消化科,浙江金华321000

出　　处：《中国病理生理杂志》2018年第11期1997-2003,共7页Chinese Journal of Pathophysiology

基　　金：浙江省科技厅课题(No.2014C33140);浙江省金华市科技计划项目(No.2013-3-060)

摘　　要：目的:本研究旨在寻找胃癌转移相关微小RNA(microRNA,miRNA,miR),揭示其对胃癌细胞生物学功能的影响,并探讨联合阻断候选miRNA在胃癌治疗中的临床应用价值。方法:收集发生淋巴结转移及无转移患者的胃癌标本各3例,采用miRNA表达芯片筛选转移相关的候选miRNA;将锁核酸修饰的候选miRNA的反义寡核苷酸转染BGC-823胃癌细胞株,运用CCK-8法、流式细胞术、划痕实验及Transwell迁移实验分析候选miRNA抑制前后胃癌细胞生物学功能的变化;构建多西环素诱导多重靶向候选miRNA的裸鼠移植瘤模型,观察联合靶向阻断候选miRNA后,肿瘤细胞体内生长情况。结果:miRNA表达芯片发现miR-29b、miR-92b及miR-106b在发生淋巴结转移患者的胃癌组织最高,并将它们确定为胃癌转移相关候选miRNA;分别在BGC-823细胞中抑制上述miRNA,可导致细胞活力减弱,凋亡诱导增加,迁移能力显著下降(P <0. 05);同时,体内联合阻断miR-29b/92b/106b,裸鼠移植瘤的形成较对照组显著减少。结论:miR-29b、miR-92b及miR-106b与胃癌细胞的迁移有关,联合阻断上述miRNA可明显抑制胃癌细胞体内外生长。这3个miRNA可能作为潜在的治疗靶点。AIM:To investigate the metastasis-associated microRNAs(miRNAs,miR)in gastric cancer,and to determine their biological and therapeutic roles in this malignancy.METHODS:The tumor tissue samples from gastric cancer patients with or without lymph node metastasis were collected(n=3 each).miRNA microarray was used to determine the metastasis-associated miRNAs.Gastic cancer cell line BGC-823 was transfected with locked nucleic acidmodified antisense oligonucleotides of candidate miRNAs and subsequently used for functional assays including CCK-8 assay,flow cytometry,wound healing assay and Transwell migration assay.Furthermore,the in vivo xenograft mice were used to evaluate the tumor suppressive effect of collaborative inhibition of the candidate miRNAs.RESULTS:miR-29b,miR-92b and miR-106b were up-regulated in the tumor tissues from the gastric cancer patients with lymph node metastasis.The functional assays showed that blockage of miR-29b,miR-92b and miR-106b by antisense oligonucleotides in the BGC-823 cells significantly inhibited cell growth and migration,and induced apoptosis.Furthermore,the collaborative inhibition of these triple miRNAs remarkably suppressed tumor growth in vivo.CONCLUSION:miR-29b,miR-92b and miR-106b are metastasis-associated miRNAs.These miRNAs may provide promising therapeutic targets in gastric cancer.

关 键 词：小RNA-29b 微小RNA-92b 微小RNA-106b 胃癌 迁移 

分 类 号：R735.2[医药卫生—肿瘤] R363.2[医药卫生—临床医学]