Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.
DNA Cell Biol. 2020 Oct;39(10):1825-1837. doi: 10.1089/dna.2019.5320. Epub 2020 Aug 14.
The objective of this study was to identify the key circular RNAs (circRNAs) related to the development of colon cancer. High-throughput RNA sequencing on eight early-stage (ES) and eight later stage (LS) colon tumor tissues, and eight normal tissues, was performed. Differentially expressed circRNAs and differentially expressed mRNAs were identified. Functional enrichment analysis and the miRNA-circRNA-mRNA network were performed. In addition, the differential expression levels of key circRNAs were verified using real-time quantitative PCR (qPCR). In total, 408, 472, and 278 differentially expressed circRNAs were identified in ES versus normal control (N), LS versus N, and LS versus ES groups, respectively. Functional enrichment analysis showed that circ_052666 was significantly enriched in "extracellular matrix/receptor interaction"; circ_022743 was remarkably enriched in "neurotrophin signaling pathway"; and circ_004452 was observably enriched in "TGF-β signaling pathway." Moreover, key miRNA-circRNA-mRNA relationships, such as hsa-miR-29b/c-3p-circ_052666-COL1A1 and hsa-miR-1294-circ_004452-left-right determination factor 1 (LEFTY1), were identified. Furthermore, qPCR showed consistent results with RNA sequencing. Our findings indicate that key circRNAs, such as circ_022743, circ_052666, and circ_004452, may be involved in colon cancer development, and could be used as potential biomarkers for the diagnosis and treatment of this disease.
本研究旨在鉴定与结肠癌发展相关的关键环状 RNA(circRNA)。对 8 例早期(ES)和 8 例晚期(LS)结肠肿瘤组织以及 8 例正常组织进行高通量 RNA 测序。鉴定差异表达的 circRNA 和差异表达的 mRNA。进行功能富集分析和 miRNA-circRNA-mRNA 网络分析。此外,使用实时定量 PCR(qPCR)验证关键 circRNA 的差异表达水平。共鉴定出 ES 与正常对照(N)、LS 与 N 以及 LS 与 ES 组相比分别有 408、472 和 278 个差异表达的 circRNA。功能富集分析表明,circ_052666 在“细胞外基质/受体相互作用”中显著富集;circ_022743 在“神经生长因子信号通路”中显著富集;circ_004452 在“TGF-β 信号通路”中显著富集。此外,鉴定出关键的 miRNA-circRNA-mRNA 关系,如 hsa-miR-29b/c-3p-circ_052666-COL1A1 和 hsa-miR-1294-circ_004452-left-right determination factor 1 (LEFTY1)。此外,qPCR 与 RNA 测序结果一致。我们的研究结果表明,circ_022743、circ_052666 和 circ_004452 等关键 circRNA 可能参与结肠癌的发展,可作为诊断和治疗该疾病的潜在生物标志物。