Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou City, PR. China.
Cell Cycle. 2020 Nov;19(22):3127-3139. doi: 10.1080/15384101.2020.1834301. Epub 2020 Oct 22.
The effect of circular RNA MTO1 (circMTO1) signaling on the expression of miR-199a-3p in gastric carcinoma cells, and its effect on proliferation and apoptosis of gastric cancer cells were investigated in this study. RT-qPCR was performed to detect the expression levels of circMTO1 and miR-199a-3p in the cell lines and tissues of gastric cancer. The effect of circMTO1 and miR-199a-3p on the growth and apoptosis of tumor cells was detected by BrdU incorporation and Annexin V/PI staining. Target gene prediction and screening, and luciferase reporter assays were performed to validate downstream interested genes of circMTO1 and miR-199a-3p. The expression levels of miR-199a-3p target gene PAWR (named as PRKC apoptosis WT1 Regulator Protein) was measured by RT-qPCR and Western blotting. Tumor changes in mice were detected by transfecting circMTO1. The expression of circMTO1 was significantly downregulated in the cell lines and tissues of gastric cancer, and low expression levels of circMTO1 were closely associated with poor prognosis. Overexpression of circMTO1 inhibited tumor growth, enhanced apoptosis rate and decreased cell invasion and migration. There was a significant negative relationship between the expression levels of circMTO1 and miR-199a-3p in gastric cancer tissues. Inhibiting miR-199a-3p expression or overexpression of PAWR could decrease the promotive effects of knockdown of circMTO1 on the progression of gastric cancer, and a positive relationship was established between the expression of circMTO1 and PAWR. circMTO1 can regulate the growth of gastric cancer cells by regulating miR-199a-3p/PAWR axis, thus inhibiting the development and progression of gastric cancer. GC: Gastric cancer; circ RNA: Circular RNA; MTO1: mitochondrial translation optimized 1 homolog.
本研究旨在探讨环状 RNA MTO1(circMTO1)信号对胃癌细胞中 miR-199a-3p 表达的影响,以及其对胃癌细胞增殖和凋亡的影响。采用 RT-qPCR 检测胃癌细胞系和组织中 circMTO1 和 miR-199a-3p 的表达水平。通过 BrdU 掺入和 Annexin V/PI 染色检测 circMTO1 和 miR-199a-3p 对肿瘤细胞生长和凋亡的影响。进行靶基因预测和筛选,并进行荧光素酶报告基因检测验证 circMTO1 和 miR-199a-3p 的下游靶基因。采用 RT-qPCR 和 Western blot 检测 miR-199a-3p 靶基因 PAWR(命名为 PRKC apoptosis WT1 Regulator Protein)的表达水平。通过转染 circMTO1 检测小鼠肿瘤变化。胃癌细胞系和组织中 circMTO1 的表达明显下调,低表达水平的 circMTO1 与不良预后密切相关。过表达 circMTO1 抑制肿瘤生长,增强凋亡率,降低细胞侵袭和迁移。胃癌组织中 circMTO1 的表达与 miR-199a-3p 的表达呈显著负相关。抑制 miR-199a-3p 的表达或过表达 PAWR 可降低 circMTO1 敲低对胃癌进展的促进作用,circMTO1 的表达与 PAWR 呈正相关。circMTO1 可以通过调节 miR-199a-3p/PAWR 轴来调节胃癌细胞的生长,从而抑制胃癌的发展和进展。GC:胃癌;circRNA:环状 RNA;MTO1:线粒体翻译优化 1 同源物。