Circular RNA (circRNA) has been reported to have great scientific significance and clinical value in multiple cancers including colorectal cancer (CRC). However, the biological function of most circRNAs in CRC is still in its infancy. Herein, we discovered the differential expressed circRNAs (DECs) between CRC tissues and matched adjacent using deep RNA sequencing and further confirmed the DECs expression by combining with another Gene Expression Omnibus dataset. Furthermore, we validated the expression of the top four upregulated circRNAs (hsa_circ_0030632, hsa_circ_0004887, hsa_circ_0001550, and hsa_circ_0001681) in both of paired CRC tissues and CRC cell lines. Then, a circRNA/microRNA/messenger RNA regulatory network was established and the Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed these four circRNAs participated in various biological processed including apoptotic process and multiple metabolic processes. Moreover, based on the regulatory network, three bioactive compounds (pergolide, pivampicillin, and methylergometrine) for the treatment of CRC were also found. In conclusion, this study improved our understanding of circRNAs and may also facilitate the finding of promising targets and biomarkers in CRC.

中文翻译：

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功能性circRNA/miRNA/mRNA调控网络的鉴定，探索结直肠癌的前瞻性治疗策略。

据报道，环状RNA（circRNA）在包括结直肠癌（CRC）在内的多种癌症中具有重要的科学意义和临床价值。然而，大多数 circRNA 在 CRC 中的生物学功能仍处于起步阶段。在此，我们使用深度RNA测序发现了CRC组织之间差异表达的circRNA（DEC）并匹配了相邻组织，并通过结合另一个基因表达综合数据集进一步证实了DEC的表达。此外，我们验证了配对 CRC 组织和 CRC 细胞系中前四种上调的 circRNA（hsa_circ_0030632、hsa_circ_0004887、hsa_circ_0001550 和 hsa_circ_0001681）的表达。然后，建立了circRNA/microRNA/messenger RNA调控网络，基因本体分析和京都基因与基因组百科全书通路富集分析显示这四种circRNA参与了包括细胞凋亡过程和多种代谢过程在内的多种生物过程。此外，基于调控网络，还发现了三种用于治疗结直肠癌的生物活性化合物（培高利特、匹氨西林和甲基麦角新碱）。总之，这项研究提高了我们对 circRNA 的理解，也可能有助于发现 CRC 有前景的靶点和生物标志物。