Circ_0007142吸附miR-647调控CCR8基因促进胃癌细胞的上皮-间质转化和侵袭

doi:10.19401/j.cnki.1007-3639.2021.08.004

中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (8): 714-724.doi: 10.19401/j.cnki.1007-3639.2021.08.004

Circ_0007142吸附miR-647调控CCR8基因促进胃癌细胞的上皮-间质转化和侵袭

张学成 ¹ ，关晓辉 ²

1. 吉林市中心医院消化科，吉林吉林 132000 ；
2. 北华大学附属医院消化内科，吉林吉林 132000

出版日期:2021-08-30 发布日期:2021-09-03
通信作者: 关晓辉 E-mail：87173680@qq.com
基金资助:
吉林省卫生厅科技计划项目（2013S004）。

Circ_0007142 accelerates epithelial-mesenchymal transition and invasion of gastric cancer cells through sponging miR-647 and regulating CCR8 gene

ZHANG Xuecheng¹ , GUAN Xiaohui ²

1. Department of Gastroenterology, Beihua University, Jilin Central Hospital, Jilin 132000, Jilin Province, China; 2. Department of Gastroenterology, Affiliated Hospital of Beihua University, Jilin 132000, Jilin Province, China

Published:2021-08-30 Online:2021-09-03
Contact: GUAN Xiaohui E-mail: 87173680@qq.com

摘要/Abstract

摘要： 背景与目的：胃癌是常见的消化道恶性肿瘤，circ_0007142被证实为结直肠癌的致癌因子，能促进结直肠癌的进展。探究circ_0007142吸附miR-647调控CCR8基因对胃癌细胞上皮-间质转化（epithelial-mesenchymal transition，EMT）和侵袭的影响。方法：采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）对组织和细胞中circ_0007142、miR-647、CCR8的表达进行检测；采用荧光原位杂交（fluorescence in situ hybridization，FISH）实验鉴定circ_0007142的亚细胞定位；采用双荧光素酶报告基因实验和RNA免疫沉淀（RNA immunoprecipitation，RIP）实验验证circ_0007142和miR-647、miR-647和CCR8的相互关系；采用transwell、克隆形成实验和蛋白质印迹法（Western blot）检测细胞的侵袭能力、集落形成能力和EMT程度；BALB/c裸小鼠移植瘤实验检测circ_0007142在体内的促瘤作用。结果：Circ_0007142和CCR8在胃癌组织和细胞中过表达，miR-647在胃癌组织和细胞中低表达。circ_0007142发挥分子海绵的作用抑制miR-647的表达，而miR-647通过与CCR8 mRNA的3’-UTR结合抑制CCR8表达。敲减circ_0007142或者上调miR-647的表达都可以抑制胃癌细胞的侵袭、克隆形成与EMT。而敲减circ_0007142或上调miR-647表达对胃癌细胞的影响能够被miR-647 inhibitor 或CCR8过表达部分逆转（P均<0.05）。此外，在胃癌细胞中敲减circ_0007142的表达能够抑制肿瘤的体内生长。结论：Circ_0007142吸附miR-647上调CCR8的表达，进而促进胃癌细胞的EMT和侵袭，促进胃癌的进展。

关键词: Circ_0007142, miR-647, CCR8, 胃癌, 上皮-间质转化, 侵袭

Abstract: Background and purpose: Gastric cancer is the most common malignant tumor of digestive tract. Circ_0007142 has been proved to be a carcinogenic factor of colorectal cancer and can promote the progression of colorectal cancer. This study aimed to explore the effects of circ_0007142 on epithelial-mesenchymal transition (EMT) and invasion of gastric cancer cells via absorbing miR-647 and then regulating CCR8 gene. Methods: Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the expressions of circ_0007142, miR-647 and CCR8 in gastric cancer tissues and cells. Fluorescence in situ hybridization (FISH) experiment was adopted to determine the subcellular localization of circ_0007142. Dual luciferase reporter experiment and RNA immunoprecipitation (RIP) assay were used to confirm the targeting relationship of circ_0007142 and miR-647 as well as miR-647 and CCR8. Transwell assay, clone formation assay and Western blot were used to test the cell invasion ability, clonality and EMT respectively. Tumor xenograft in BALB/c nude mice was performed to detect tumorigenicity of circ_0007142 in vivo. Results: Overexpressions of circ_0007142 and CCR8 and downregulation of miR-647 were detected in gastric cancer tissues and cells. Circ_0007142 acted as a molecular sponge to inhibit the expression of miR-647, at the same time, miR-647 inhibited the expression of CCR8 by binding with the 3'-UTR of CCR8 mRNA. Knockdown of circ_0007142 or overexpression of miR-647 inhibited the invasion, colony formation and EMT of gastric cancer cells. However, the effects of circ_0007142 inhibition or miR-647 overexpression on gastric cancer cells were partially reversed by miR-647 inhibitor or CCR8 overexpression (all P<0.05). Moreover, knockdown of circ_0007142 in gastric cancer cells inhibited the tumor growth in vivo. Conclusion: Circ_0007142 upregulates the expression of CCR8 via sponging miR-647, which subsequently accelerates the EMT and invasion of gastric cancer cells and promotes the progression of gastric cancer.

Key words: Circ_0007142, miR-647, CCR8, Gastric cancer, Epithelial-mesenchymal transition, Invasion

张学成, 关晓辉 . Circ_0007142吸附miR-647调控CCR8基因促进胃癌细胞的上皮-间质转化和侵袭[J]. 中国癌症杂志, 2021, 31(8): 714-724.

ZHANG Xuecheng , GUAN Xiaohui . Circ_0007142 accelerates epithelial-mesenchymal transition and invasion of gastric cancer cells through sponging miR-647 and regulating CCR8 gene[J]. China Oncology, 2021, 31(8): 714-724.

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Circ_0007142吸附miR-647调控CCR8基因促进胃癌细胞的上皮-间质转化和侵袭

Circ_0007142 accelerates epithelial-mesenchymal transition and invasion of gastric cancer cells through sponging miR-647 and regulating CCR8 gene

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