circRNA-ZKSCAN1通过调节miR-628-5p/UPF1轴促进结直肠癌细胞增殖、迁移和侵袭  

circRNA-ZKSCAN1 Promotes Colorectal Cancer Proliferation, Migration and Invasion by Regulating the miR-628-5p/UPF1 Axis

作　　者：强勇 王斐然[2] 张小风 易汪洋 叶龙 唐翀[3] Qiang Yong;Wang Feiran;Zhang Xiaofeng(Department of General Surgery,Jingmen Second People’s Hospital,Jingmen 448000,China;Department of General Surgery,Affiliated Hospital of Nantong University,Nantong 226000,China)

机构地区：[1]荆门市第二人民医院普外科,荆门448000 [2]南通大学附属医院普外科,南通226000 [3]南通市第一人民医院普外科,南通226000

出　　处：《华中科技大学学报（医学版）》2022年第3期326-333,共8页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省自然科学基金资助项目(No.2020CFB712)。

摘　　要：目的 探讨circRNA-ZKSCAN1(circZKSCAN1)在结直肠癌细胞增殖、迁移和侵袭中的作用及其机制。方法 收集结直肠癌临床组织样本和细胞系,通过实时荧光定量PCR(qRT-PCR)检测circZKSCAN1的表达。利用CCK-8、划痕实验和Transwell实验检测circZKSCAN1在结直肠癌细胞增殖、迁移和侵袭中的作用。通过荧光素酶报告基因实验、qRT-PCR和Western blot检测分析circZKSCAN1、miR-628-5p和UPF1之间的调控关系。结果 circZKSCAN1在结直肠癌组织和细胞中的表达显著增加。敲降circZKSCAN1后可抑制HCT116细胞增殖能力,并抑制HCT116细胞的迁移和侵袭能力。circZKSCAN1被发现充当miR-628-5p的分子海绵,miR-628-5p的过表达明显抑制了野生型(WT)circZKSCAN1的转录活性,并且抑制circZKSCAN1表达增加了miR-628-5p表达水平。同时,结直肠癌患者癌组织中miR-628-5p的表达水平也降低,并与circZKSCAN1表达呈负相关。circZKSCAN1可以靶向调控miR-628-5p,下调miR-628-5p表达逆转了抑制circZKSCAN1表达对HCT116细胞增殖、迁移和侵袭的作用。此外,在过表达miR-628-5p或抑制circZKSCAN1后,UPF1表达显著降低,但当circZKSCAN1和miR-628-5p均受到抑制时,其表达得以恢复。结论 circZKSCAN1在结直肠癌中的表达显著增加,circZKSCAN1可能通过miR-628-5p/UPF1途径促进结直肠癌细胞的增殖、迁移和侵袭能力,是结直肠癌分子靶向治疗的潜在靶点。Objective To investigate the role of circRNA-ZKSCAN1(circZKSCAN1)in the proliferation, migration, and invasion of colorectal cancer cells, and to explore possible mechanism.Methods Clinical tissue samples and cells were collected, and the expression of circZKSCAN1 was detected by qRT-PCR.CCK-8,scratch test, and Transwell assay were performed to detect the role of circZKSCAN1 in the proliferation, migration, and invasion of colorectal cancer cells.The regulatory relationship between circZKSCAN1,miR-628-5 p, and UPF1 was determined by luciferase reporter assay, qRT-PCR,and Western blotting.Results The expression of circZKSCAN1 in colorectal cancer tissues and cells increased significantly.Knockdown of circZKSCAN1 inhibited the proliferation, migration, and invasion of HCT116 cells.circZKSCAN1 was found to be a molecular sponge of miR-628-5 p.Overexpression of miR-628-5 p significantly inhibited the luciferase activity of wild-type(WT)circZKSCAN1,and inhibition of circZKSCAN1 expression increased the expression level of miR-628-5 p.In addition, the expression level of miR-628-5 p was also downregulated among colorectal cancer patients and was negatively correlated with the expression of circZKSCAN1.circZKSCAN1 could affect miR-628-5 p level by targeted regulation, and downregulation of miR-628-5 p expression reversed the effects of circZKSCAN1 inhibited expression on the proliferation, migration, and invasion of HCT116 cells.Moreover, UPF1 expression decreased significantly after upregulation of miR-628-5 p or downregulation of circZKSCAN1,but its expression was restored when both circZKSCAN1 and miR-628-5 p were inhibited.Conclusion The expression of circZKSCAN1 in colorectal cancer is significantly increased.In addition, circZKSCAN1 may promote the proliferation, migration, and invasion of colorectal cancer cells through the miR-628-5 p/UPF1 pathway, which is a potential target for molecular targeted therapy of colorectal cancer.

关 键 词：结直肠癌 circRNA-ZKSCAN1 miR-628-5p UPF1 增殖 迁移 侵袭 

分 类 号：R735.3[医药卫生—肿瘤]