Chemoresistance is a major clinical obstacle for the treatment of colorectal cancer (CRC). Circular RNAs (circRNAs) are a new type of non-coding RNA that participated in the development of chemoresistance. However, the profiles and effects of circRNAs in 5-fluorouracil (5-Fu) and cisplatin resistance of CRC are still unclear and need to be elucidated. In the present study, the profiles of circRNAs in CRC chemoresistant (HCT8/5-Fu and HCT8/DDP) and chemosensitive (HCT8) cell lines were identified via RNA-sequencing. In total, 48 and 90 differentially expressed (DE)-circRNAs were detected in HCT8/5-Fu and HCT8/DDP cell lines, respectively. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were conducted on the host genes of DE-circRNAs; the results showed that the most significant enrichment pathways in HCT8/5-Fu and HCT8/DDP cell lines were base excision repair and Hippo signaling pathway, respectively. In addition, 11 common DE-circRNAs in the two drug-resistant cell lines (two are upregulated and nine are downregulated) were screened and verified by quantitative real-time PCR; hsacirc_023607 and hsacirc_007420 were found to be the circRNAs with the highest upregulation and downregulation fold changes. However, functional studies showed hsacirc_023607 has no effect on CRC chemoresistance. Therefore, the regulatory networks of targeted miRNAs related to 5-Fu or cisplatin resistance were predicted and constructed, in which hsacirc_002482 was identified as a hub gene, and its overexpression could suppress HCT8/5-Fu and HCT8/DDP cell proliferation and promote cell apoptosis, and enhance cell chemosensitivity. Taken together, these results of the study suggested that hsacirc_002482 may play important roles in chemoresistance of CRC.

化疗耐药是结直肠癌（CRC）治疗的主要临床障碍。环状RNA（circRNA）是一种新型的非编码RNA，参与了耐药性的发展。然而，circRNAs 在 5-氟尿嘧啶 (5-Fu) 和 CRC 顺铂耐药中的概况和作用仍不清楚，需要阐明。在本研究中，确定了 CRC 化学抗性（HCT8/5-Fu 和 HCT8/DDP）和化学敏感（HCT8）细胞系中的 circRNA 谱通过RNA 测序。总共分别在 HCT8/5-Fu 和 HCT8/DDP 细胞系中检测到 48 和 90 个差异表达（DE）-circRNA。对DE-circRNAs宿主基因进行Gene Ontology富集和Kyoto Encyclopedia of Genes and Genomes通路分析；结果表明，HCT8/5-Fu和HCT8/DDP细胞系中最显着的富集途径分别是碱基切除修复和Hippo信号通路。此外，通过定量实时PCR筛选并验证了两种耐药细胞系中的11种常见DE-circRNA（2种上调，9种下调）；hsacirc_023607 和 hsacirc_007420 被发现是具有最高上调和下调倍数变化的 circRNA。然而，功能研究表明 hsacirc_023607 对 CRC 化学抗性没有影响。所以，预测并构建了与5-Fu或顺铂耐药相关的靶向miRNA调控网络，其中hsacirc_002482被鉴定为枢纽基因，其过表达可抑制HCT8/5-Fu和HCT8/DDP细胞增殖，促进细胞凋亡，并增强细胞化学敏感性。综上所述，这些研究结果表明 hsacirc_002482 可能在 CRC 的化学抗性中起重要作用。