Li Kai, Cao Jiacheng, Zhang Zitong, Chen Keyan, Ma Tieliang, Yang Wenjie, Yang Shikun, Rao Jianhua, Zhang Kai
Department of General Surgery, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China.
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Oncol. 2020 Nov 11;10:598256. doi: 10.3389/fonc.2020.598256. eCollection 2020.
Circular RNAs (circRNAs) have important regulatory roles in the development of various cancers. However, the biological functions and potential molecular mechanisms of circRNAs in hepatocellular carcinoma (HCC) are still unclear. In this study, we investigated the role of a new circRNA-circGSK3B (hsa_circ_0003763) and its molecular mechanism in HCC. We found that circGSK3B was highly expressed in HCC tissues and HCC cell lines. Additionally, the expression level of circGSK3B significantly correlated with HCC tumor size and vascular invasion. Functionally, we confirmed that circGSK3B can promote the proliferation, migration, and invasion of HCC cells and . In terms of mechanism, we demonstrated that circGSK3B acts as a miR-1265 sponge, positively regulates the target gene , and promotes the reprogramming of glutamine metabolism, thereby promoting the progression of HCC. Finally, the classic RNA binding protein QKI was observed to participate in the biogenesis of circGSK3B. In summary, we proved that the circGSK3B-miR-1265- axis can promote the proliferation, migration, invasion of HCC cells, indicating that circGSKB may serve as a promising diagnostic and prognostic marker in HCC.
环状RNA(circRNAs)在多种癌症的发生发展中具有重要的调控作用。然而,circRNAs在肝细胞癌(HCC)中的生物学功能和潜在分子机制仍不清楚。在本研究中,我们探究了一种新的环状RNA——circGSK3B(hsa_circ_0003763)在HCC中的作用及其分子机制。我们发现circGSK3B在HCC组织和HCC细胞系中高表达。此外,circGSK3B的表达水平与HCC肿瘤大小和血管侵犯显著相关。在功能方面,我们证实circGSK3B可促进HCC细胞的增殖、迁移和侵袭。在机制方面,我们证明circGSK3B作为miR-1265的海绵,正向调节靶基因,促进谷氨酰胺代谢重编程,从而促进HCC进展。最后,观察到经典的RNA结合蛋白QKI参与circGSK3B的生物合成。总之,我们证明circGSK3B-miR-1265轴可促进HCC细胞的增殖、迁移和侵袭,表明circGSKB可能是HCC中有前景的诊断和预后标志物。