Department of Urology, Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Cancer Med. 2021 Nov;10(22):8210-8221. doi: 10.1002/cam4.4311. Epub 2021 Sep 27.
Circular RNAs (circRNAs) are novel biomarkers of various cancers. CircRNAs can sponge miRNAs and regulate target mRNAs, which was called competing endogenous RNAs (ceRNA). This study was designed to identify circRNAs related to patients with clear cell renal cell carcinoma (ccRCC) and the first to select three independent Gene Expression Omnibus microarrays covering circRNAs, miRNAs, and mRNAs for multiple analyses. The data of clinical cases applied in our study were obtained from The Cancer Genome Atlas. We successfully conducted a circRNA/miRNA/mRNA ceRNA network related to ccRCC patients via R software and Cytoscape including 8 circRNAs, 6 miRNAs, and 49 mRNAs. The prognosis-associated subnet covered 8 circRNAs, 6 miRNAs, and 22 mRNAs. Quantitative real-time PCR was applied to measure our prediction in three renal cell lines and 23 pairs of tissues. Small interfering RNA targeting the back-splice region of hsa_circ_0001167 was further implied to confirm the regulation. Ultimately, hsa_circ_0001167/hsa-miR-595/CCDC8 regulatory axis was identified in this study, which may serve as prognostic indicators. Lower levels of hsa_circ_0001167 and CCDC8 were potentially correlated with worse patient survival.
环状 RNA(circRNAs)是各种癌症的新型生物标志物。circRNAs 可以海绵吸附 miRNA 并调控靶 mRNA,这被称为竞争性内源 RNA(ceRNA)。本研究旨在鉴定与透明细胞肾细胞癌(ccRCC)患者相关的 circRNAs,并首次选择三个独立的基因表达谱微阵列涵盖 circRNAs、miRNAs 和 mRNAs 进行多项分析。应用于本研究的临床病例数据来自癌症基因组图谱。我们成功地通过 R 软件和 Cytoscape 构建了一个与 ccRCC 患者相关的 circRNA/miRNA/mRNA ceRNA 网络,其中包括 8 个 circRNAs、6 个 miRNAs 和 49 个 mRNAs。预后相关的子网络涵盖了 8 个 circRNAs、6 个 miRNAs 和 22 个 mRNAs。我们应用实时定量 PCR 在三个肾细胞系和 23 对组织中测量了我们的预测结果。进一步通过靶向 hsa_circ_0001167 反向拼接区域的小干扰 RNA 来验证调控作用。最终,在本研究中鉴定了 hsa_circ_0001167/hsa-miR-595/CCDC8 调控轴,它可能作为预后指标。hsa_circ_0001167 和 CCDC8 的水平较低与患者生存状况较差可能相关。