Yuan Dong-Feng, Wang Hao-Ran, Wang Zong-Fei, Liang Guang-Hui, Xing Wen-Qun, Qin Jian-Jun
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China; Department of Thoracic Surgery, The Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China.
Biochem Biophys Res Commun. 2021 Nov 26;580:100-106. doi: 10.1016/j.bbrc.2021.09.085. Epub 2021 Oct 3.
Circular RNAs (circRNAs) are known to regulate tumorigenesis. In this study, circRNAs microarray was used to analyze the circRNA expression in lung adenocarcinoma (LUAD) tissues, and CircRNA zinc finger MYM-type containing 4(circZMYM4) was selected for further analysis. In this study, we detected circZMYM4 expression in LUAD specimens and cell lines using RT-PCR. The expression of circZMYM4 was further verified in the GEO datasets and TCGA datasets. Gain-of-function and loss-of-function experiments were used to analyze the effects of circZMYM4 on LUAD in vivo and in vitro. The relationship between miR-587 and circZMYM4 or ODAM was predicted by bioinformatics tools and confirmed using dual-luciferase reporter assays and RNA-pull down. We found that circZMYM4 was distinctly down-regulated in LUAD tissues and cell lines. Functional assays revealed that circZMYM4 overexpression suppressed LUAD cell proliferation, metastasis and suppressed apoptosis, while miR-587 overexpression could weaken these effects. Importantly, circZMYM4 upregulated ODAM expression via sponging miR-587 to suppress LUAD progression. ODAM knockdown could reverse the repressive effect of circZMYM4 overexpression on cell proliferation, migration and invasion abilities. Overall, circZMYM4 regulates the miR-587/ODAM axis to suppress LUAD progression, which may become a potential biomarker and therapeutic target.
环状RNA(circRNAs)已知可调节肿瘤发生。在本研究中,使用环状RNA微阵列分析肺腺癌(LUAD)组织中的环状RNA表达,并选择环状RNA锌指MYM型包含4(circZMYM4)进行进一步分析。在本研究中,我们使用逆转录聚合酶链反应(RT-PCR)检测LUAD标本和细胞系中circZMYM4的表达。circZMYM4的表达在基因表达综合数据库(GEO)数据集和癌症基因组图谱(TCGA)数据集中得到进一步验证。采用功能获得和功能缺失实验分析circZMYM4在体内和体外对LUAD的影响。通过生物信息学工具预测miR-587与circZMYM4或口腔分化相关分子(ODAM)之间的关系,并使用双荧光素酶报告基因检测和RNA下拉实验进行验证。我们发现circZMYM4在LUAD组织和细胞系中明显下调。功能分析表明,circZMYM4过表达抑制LUAD细胞增殖、转移并抑制细胞凋亡,而miR-587过表达可减弱这些作用。重要的是,circZMYM4通过海绵吸附miR-587上调ODAM表达以抑制LUAD进展。敲低ODAM可逆转circZMYM4过表达对细胞增殖、迁移和侵袭能力的抑制作用。总体而言,circZMYM4通过调节miR-587/ODAM轴抑制LUAD进展,这可能成为一种潜在的生物标志物和治疗靶点。