Zhang Yan, Liu Hao, Li Wende, Yu Jiang, Li Jin, Shen Zhiyong, Ye Gentai, Qi Xiaolong, Li Guoxin
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangdong Provincial Engineering Technology Research Center of Minimally Invasive Surgery, Guangzhou, China.
Guangdong Key Laboratory of Laboratory Animal, Guangdong Laboratory Animal Monitoring Institute, Guangzhou, China.
Aging (Albany NY). 2017 Jun 27;9(6):1585-1594. doi: 10.18632/aging.101254.
Although CircRNA_100269 is a biomarker used to predict cancer recurrence, its expression and function in gastric cancer (GC) remain unknown. In this study, the expression of circRNA_100269 and its potential downstream miRNA targets were investigated. The molecular function and regulatory mechanism of circRNA_100269 in GC cell lines were also elucidated. The expression levels of circRNA_100269 and its linear isomer LPHN2 mRNA were found to be downregulated (p<0.01) in GC tissues. The target miRNA was predicted to be miR-630, whose expression was upregulated (p<0.01) and found to be negatively correlated with that of circRNA_100269 (r = -0.688) in GC tissues. Moreover, direct interaction of circRNA_100269 and miR-630 was confirmed through dual-luciferase assays. Overexpressing the circRNA_100269 plasmid inhibited cell proliferation (p<0.05). Furthermore, transfection of miR-630 mimics into cell lines overexpressing circRNA_100269 blocked the function of circRNA_100269 (p<0.05). Thus, circRNA_100269 level was downregulated in GC and correlated negatively with that of miR-630. Taken together, our results suggest that circRNA_100269 and miR-630 comprise a novel pathway that regulates proliferation of GC cells.
尽管环状RNA_100269是一种用于预测癌症复发的生物标志物,但其在胃癌(GC)中的表达和功能仍不清楚。在本研究中,我们调查了环状RNA_100269的表达及其潜在的下游miRNA靶点。同时也阐明了环状RNA_100269在GC细胞系中的分子功能和调控机制。结果发现,环状RNA_100269及其线性异构体LPHN2 mRNA的表达水平在GC组织中下调(p<0.01)。预测其靶miRNA为miR-630,其表达在GC组织中上调(p<0.01),且与环状RNA_之100269的表达呈负相关(r = -0.688)。此外,通过双荧光素酶报告基因实验证实了环状RNA_100269与miR-630之间的直接相互作用。过表达环状RNA_100269质粒可抑制细胞增殖(p<0.05)。此外,将miR-630模拟物转染到过表达环状RNA_100269的细胞系中可阻断环状RNA_100269的功能(p<0.05)。因此,环状RNA_100269水平在GC中下调,且与miR-630水平呈负相关。综上所述,我们的结果表明环状RNA_100269和miR-630构成了一条调节GC细胞增殖的新途径。