Lü Lingshuang, Sun Jian, Shi Peiyi, Kong Weimin, Xu Kun, He Biyu, Zhang Simin, Wang Jianming
Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Department of Thoracic Surgery, The First People's Hospital of Yancheng City, Yancheng, 224001, China.
Oncotarget. 2017 Jul 4;8(27):44096-44107. doi: 10.18632/oncotarget.17307.
Endogenous noncoding circular RNAs (circRNAs) have gained attention for their involvement in carcinogenesis, but their expression pattern in breast cancer has remained largely unknown. In this two-stage study, we first used an Arraystar Human circRNA Array to construct a genome-wide circRNA profile. We then selected candidate circRNAs for validation using a quantitative real-time polymerase chain reaction system. CircRNA/miRNA interactions were predicted and sequence analyses were performed. Among 1155 differentially expressed circRNAs, 715 were upregulated and 440 were downregulated in breast cancer tissues. The validation study demonstrated that hsa_circ_103110, hsa_circ_104689 and hsa_circ_104821 levels were elevated in breast cancer tissues, whereas hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were downregulated. These circRNAs targeted complementary miRNA response elements. The area under the receiver operating characteristic curve for distinguishing breast cancer was 0.82 (95% CI: 0.73-0.90) when hsa_circ_006054, hsa_circ_100219 and hsa_circ_406697 were used in combination. This study provides evidence that circRNAs are differentially expressed in breast cancer and are important in carcinogenesis because they participate in cancer-related pathways and sequester miRNAs.
内源性非编码环状RNA（circRNAs）因其参与致癌过程而受到关注，但其在乳腺癌中的表达模式仍 largely未知。在这项两阶段研究中，我们首先使用Arraystar人类circRNA阵列构建全基因组circRNA图谱。然后我们选择候选circRNAs使用定量实时聚合酶链反应系统进行验证。预测了circRNA/miRNA相互作用并进行了序列分析。在1155个差异表达的circRNAs中，715个在乳腺癌组织中上调，440个下调。验证研究表明，hsa_circ_103110、hsa_circ_104689和hsa_circ_104821在乳腺癌组织中的水平升高，而hsa_circ_006054、hsa_circ_100219和hsa_circ_406697下调。这些circRNAs靶向互补的miRNA反应元件。当联合使用hsa_circ_006054、hsa_circ_100219和hsa_circ_406697时，区分乳腺癌的受试者工作特征曲线下面积为0.82（95%CI：0.73 - 0.90）。本研究提供了证据表明circRNAs在乳腺癌中差异表达，并且在致癌过程中很重要，因为它们参与癌症相关途径并隔离miRNAs。
