Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, P.R. China.
Department of Rheumatology and Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, P.R. China.
Aging (Albany NY). 2020 May 28;12(10):9793-9806. doi: 10.18632/aging.103244.
Circular RNAs (circRNAs) play an important role in the tumorigenesis of hepatocellular carcinoma (HCC), but their specific functions in HCC remain largely unknown. Using bioinformatics analysis, we have found that the expression of circRNA hsa_circ_0003141 is significantly increased in HCC tissues. Ubiquitin-associated protein 2 (UBAP2) is the parent gene for hsa_circ_0003141, and its high expression correlates with poor overall survival rates in HCC patients. In addition, our results show that miR-1827 is a binding target of hsa_circ_0003141, and indicate that hsa_circ_0003141 regulates UBAP2 expression by sponging miR-1827 in HCC cells. Downregulation of hsa_circ_0003141 suppresses UBAP2 expression, induces apoptosis, and inhibits proliferation and invasion by HCC Huh-7 cells. Importantly, downregulation of hsa_circ_0003141 inhibits tumorigenesis in a xenograft mouse model of HCC. Together, our results indicate that hsa_circ_0003141 functions as an oncogene in HCC cells, and suggest that the hsa_circ_0003141/miR-1827/UBAP2 axis might represent a novel therapeutic option for the treatment of HCC.
环状 RNA（circRNAs）在肝细胞癌（HCC）的发生发展中发挥重要作用，但它们在 HCC 中的具体功能仍知之甚少。通过生物信息学分析，我们发现环状 RNA hsa_circ_0003141 在 HCC 组织中的表达显著升高。泛素结合蛋白 2（UBAP2）是 hsa_circ_0003141 的母基因，其高表达与 HCC 患者的总生存率降低相关。此外，我们的研究结果表明 miR-1827 是 hsa_circ_0003141 的结合靶点，并且表明 hsa_circ_0003141 通过海绵吸附 miR-1827 来调节 HCC 细胞中的 UBAP2 表达。下调 hsa_circ_0003141 可抑制 UBAP2 表达，诱导 HCC Huh-7 细胞凋亡，并抑制增殖和侵袭。重要的是，下调 hsa_circ_0003141 可抑制 HCC 裸鼠移植瘤模型中的肿瘤生成。综上所述，我们的研究结果表明 hsa_circ_0003141 在 HCC 细胞中作为癌基因发挥作用，并且 hsa_circ_0003141/miR-1827/UBAP2 轴可能代表 HCC 治疗的一种新的治疗选择。
