circ_0000267通过miR-661/NGAL轴调控胃癌进展的研究  

circ_0000267 regulates gastric cancer progression through the miR-661/NGAL axis

作　　者：韩明阳[1] 白军伟[1] 聂洁伟[1] 李媛媛[1] 张超[1] Han Mingyang;Bai Junwei;Nie Jiewei;Li Yuanyuan;Zhang Chao(Department of General Surgery,He'nan Provincial People's Hospital,Zhengzhou 450000,China)

机构地区：[1]河南省人民医院普外科,郑州450000

出　　处：《中华普通外科杂志》2022年第8期602-607,共6页Chinese Journal of General Surgery

摘　　要：目的探讨circ_0000267对胃癌细胞体外增殖、迁移、侵袭、凋亡及体内生长的影响。方法体外构建敲低circ_0000267和过表达miR-661的胃癌细胞株,采用qRT-PCR检测胃癌组织和细胞中circ_0000267、miR-661和NGAL mRNA表达,采用克隆形成、Transwell小室和流式细胞仪实验检测细胞增殖、迁移、侵袭及凋亡,Western blot检测相关蛋白表达,通过在线预测结合双荧光素酶实验和RNA pull down实验验证circ_0000267、miR-661和NGAL之间的靶向关系,裸鼠成瘤实验观察敲除circ_0000267对胃癌细胞体内生长的影响。结果circ_0000267在胃癌组织和细胞中高表达;敲低circ_0000267能够抑制胃癌细胞的增殖、迁移、侵袭,促进细胞凋亡;circ_0000267靶向miR-661,抑制miR-661能够部分逆转敲低circ_0000267对胃癌细胞的影响;NGAL是miR-661的靶基因,过表达miR-661通过抑制NGAL调控胃癌细胞的增殖、迁移、侵袭及凋亡;敲低circ_0000267靶向miR-661抑制胃癌细胞中NGAL的表达;敲低circ_0000267抑制胃癌细胞的体内生长。结论circ_0000267可能通过调控miR-661/NGAL的表达调控胃癌细胞的增殖、迁移、侵袭及凋亡,并抑制肿瘤在体内生长。Objective To investigate the effect of CIRc_0000267 on proliferation,migration,invasion and apoptosis of gastric cancer cells in vitro.Methods Gastric cancer cell lines with circ_0000267 knockdown and miR-661 overexpression were constructed in vitro,and the expressions of circ_0000267,miR-661 and NGAL mRNA in gastric cancer tissues and cells were detected by qRT-PCR.Cell proliferation,migration,invasion and apoptosis were detected by clonogenesis,Transwell chamber and flow cytometry,and related protein expression was detected by Western blot.Online prediction combined with double luciferase assay and RNA pull down assay was used to verify the targeting relationship between circ_0000267,miR-661 and NGAL.Tumogenesis assay in nude mice was used to observe the effect of circ_0000267 knockout on the growth of gastric cancer cells in vivo.Results Circ_0000267 was highly expressed in gastric cancer tissues and cells.Knockdown circ_0000267 inhibited the proliferation,migration and invasion of gastric cancer cells and promote apoptosis.Circ_0000267 targeted miR-661,and inhibition of miR-661 partially reversed the effect of circ_0000267 on gastric cancer cells.NGAL was the target gene of miR-661,and overexpression of miR-661 regulated the proliferation,migration,invasion and apoptosis of gastric cancer cells by inhibiting NGAL.Knockdown circ_0000267 targeting miR-661 inhibited NGAL expression in gastric cancer cells;Knockdown circ_0000267 inhibited the growth of gastric cancer cells in vivo.Conclusions Circ_0000267 may regulate the proliferation,migration,invasion and apoptosis of gastric cancer cells and inhibit the growth of tumors in vivo by regulating the expression of miR-661/NGAL.

关 键 词：胃肿瘤 细胞增殖 肿瘤侵袭 细胞凋亡 

分 类 号：R735.2[医药卫生—肿瘤]