Key Laboratory of Environmental Medical Engineering and Education Ministry, Nanjing Public Health College, Southeast University, Nanjing, China.
Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, China.
Bioengineered. 2022 Apr;13(4):8277-8290. doi: 10.1080/21655979.2022.2053796.
Gastric cancer (GC) is one of the most common malignancies in the world, and effective therapeutic targets need to be identified for this type of cancer. In this study, circular RNA (circRNA) microarray analysis was utilized to screen differentially expressed circRNA in GC. Using quantitative reverse transcription polymerase chain reaction (qRT-PCR), hsa_circ_0000081 (circRNA-0000081) expression was found to be up-regulated in tissues and cells and was negative correlated with patients' survival time. RNase R and Actinomycin D assays indicated that circRNA-0000081 was significantly more resistant to R enzyme and had a longer half-life than linear RNA. Moreover, the knockdown or overexpression of circRNA-000081 could influence the proliferation, migration, and invasion potential of GC. Finally, dual luciferase reporter, RNA immunoprecipitation, qRT-PCR, and western blotting assays were used to verify the targeting relationship between circRNA-000081 and miRNA-423-5p or miRNA-423-5p and 3-phosphoinositide-dependent kinase 1 (PDPK1). In conclusion, circRNA-0000081 promotes the function of GC through sponging hsa-miR-423-5p to influence PDPK1 expression, which has a promising therapeutic potential for treating patients with GC.
胃癌(GC)是世界上最常见的恶性肿瘤之一,需要为这种癌症确定有效的治疗靶点。在本研究中,利用环状 RNA(circRNA)微阵列分析筛选 GC 中差异表达的 circRNA。通过定量逆转录聚合酶链反应(qRT-PCR)发现,hsa_circ_0000081(circRNA-0000081)在组织和细胞中表达上调,与患者的生存时间呈负相关。RNase R 和 Actinomycin D 测定表明,circRNA-0000081 对 R 酶的抗性显著增强,半衰期长于线性 RNA。此外,circRNA-000081 的敲低或过表达可影响 GC 的增殖、迁移和侵袭能力。最后,双荧光素酶报告、RNA 免疫沉淀、qRT-PCR 和 Western blot 测定用于验证 circRNA-000081 与 miRNA-423-5p 或 miRNA-423-5p 与 3-磷酸肌醇依赖性激酶 1(PDPK1)之间的靶向关系。总之,circRNA-0000081 通过海绵吸附 hsa-miR-423-5p 促进 GC 的功能,从而影响 PDPK1 的表达,这为治疗 GC 患者提供了有前景的治疗潜力。