Li Rizeng, Wu BinBin, Xia Jianfu, Ye Lechi, Yang Xiaoping
Department of Colorectal Surgery, Wenzhou Central Hospital, Wenzhou 325000, People's Republic of China.
Department of General Surgery, The Second People's Hospital of Pingyang County, Wenzhou 325000, People's Republic of China.
Cancer Manag Res. 2019 Jul 23;11:6887-6893. doi: 10.2147/CMAR.S212180. eCollection 2019.
Circular RNAs (circRNAs) are recently identified new noncoding RNAs and play an important role in tumorigenesis. Previous studies have indicated that hsa_circRNA_102958 is a potential diagnostic indicator in gastric cancer. However, its role in colorectal cancer (CRC) is poorly understood. qRT-PCR and ISH were used to test gene expression in tissues. Survival rate was analzyed by Kaplan-Meier curve. Luciferase reporter assay was used to determine the interaction between circRNA and miRNA or between miRNA and mRNA. Western blotting was used to test protein expression. CCK8 and colony formation assay was used to analyze proliferation. Transwell assay was used for migration and invasion determination. In our research, we found that hsa_circRNA_102958 expression was significantly increased in CRC tissues, compared to adjacent normal controls. Increased hsa_circRNA_102958 levels in CRC patients indicated a poor prognosis. The effects of hsa_circRNA_102958 on CRC cell proliferation, migration and invasion were then determined by CCK8, colony formation and Transwell assays. We showed that hsa_circRNA_102958 silencing markedly suppressed CRC growth, migration and invasion. Furthermore, hsa_circRNA_102958 was identified as a sponge for miR-585. We demonstrated that hsa_circRNA_102958 promoted CDC25B expression through inhibiting miR-585 in CRC. Rescue assays illustrated that CDC25B overexpression reversed the suppressive effects of hsa_circRNA_102958 silencing on CRC. Taken together, our findings revealed the novel oncogenic roles of hsa_circRNA_102958 in CRC through miR-585/CDC25B axis.
环状RNA(circRNAs)是最近发现的新型非编码RNA,在肿瘤发生过程中发挥重要作用。先前的研究表明,hsa_circRNA_102958是胃癌的潜在诊断指标。然而,其在结直肠癌(CRC)中的作用尚不清楚。采用qRT-PCR和ISH检测组织中的基因表达。通过Kaplan-Meier曲线分析生存率。荧光素酶报告基因检测用于确定circRNA与miRNA之间或miRNA与mRNA之间的相互作用。蛋白质免疫印迹法用于检测蛋白质表达。CCK8和集落形成试验用于分析增殖情况。Transwell试验用于测定迁移和侵袭能力。在我们的研究中,我们发现与相邻正常对照相比,hsa_circRNA_102958在CRC组织中的表达显著增加。CRC患者中hsa_circRNA_102958水平升高表明预后不良。然后通过CCK8、集落形成和Transwell试验确定hsa_circRNA_102958对CRC细胞增殖、迁移和侵袭的影响。我们发现hsa_circRNA_102958沉默显著抑制CRC的生长、迁移和侵袭。此外,hsa_circRNA_102958被鉴定为miR-585的海绵。我们证明hsa_circRNA_102958通过抑制CRC中的miR-585促进CDC25B表达。挽救试验表明,CDC25B过表达逆转了hsa_circRNA_102958沉默对CRC的抑制作用。综上所述,我们的研究结果揭示了hsa_circRNA_102958通过miR-585/CDC25B轴在CRC中的新型致癌作用。