Circ-PRMT5 enhances the proliferation, migration and glycolysis of hepatoma cells by targeting miR-188-5p/HK2 axis
Circ-PRMT5 enhances the proliferation, migration and glycolysis of hepatoma cells by targeting miR-188-5p/HK2 axis
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DOI：
10.1016/j.aohep.2020.01.002
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发表时间：
2020-05-01
影响因子：
3.8
通讯作者：
Li, Peng
中科院分区：
文献类型：
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作者：
Ding, Zhenghua;Guo, Li;Li, Peng
导言和目标：环状RNA（circRNA）已被证明是包括肝细胞癌（HCC）在内的人类癌症的关键调节因子。尽管如此，circ-PRMT 5在肝癌中的作用仍然很大程度上未知。患者或材料和方法：采用实时定量聚合酶链反应（RT-qPCR）来评估肝癌组织和细胞中circ-PRMT 5、miR-188- 5 p和抗己糖激酶II（HK 2）的表达水平。分别用MTT法、transwell迁移实验和试剂盒检测细胞增殖、迁移和糖酵解。通过生物信息学数据库、双荧光素酶报告基因分析和RNA免疫沉淀（RIP）分析miR-188- 5 p与circ-PRMT 5或HK 2的相互作用关系。Western blot分析HK 2的表达水平。结果：Circ-PRMT 5在肝癌组织和细胞中的表达高于对照组。此外，功能丧失实验表明，沉默circ-PRMT 5可以抑制体外增殖、迁移、糖酵解和体内肿瘤生长。此外，我们还证实了circ-PRMT 5的过表达消除了由上调miR-188- 5 p诱导的对HCC细胞的影响。此外，miR-188- 5 p的过表达可抑制HCC的发生发展。更重要的是，HK 2是miR-188- 5 p的靶基因，miR-188- 5 p通过与HK 2特异性结合，调控肝癌细胞的增殖、迁移、糖酵解等。结论：circ-PRMT 5可能通过miR-188 - 5 p/HK 2轴在肝癌细胞增殖、迁移、糖酵解等过程中发挥重要作用，提示circ-PRMT 5可能成为肝癌治疗的潜在靶点。(c)2020年丰达西翁临床医学，A.C.由Elsevier Espana出版，S.L.U.这是一个在CC BY-NC-ND许可证下的开放获取文章（http：//creativecommons.org/licenses/by-nc-nd/4.0/）。
Introduction and objectives: Circular RNA (circRNA) has been demonstrated as a critical regulator in human cancer, including hepatocellular carcinoma (HCC). Nevertheless, the role of circ-PRMT5 in HCC remains largely unknown.Patients or materials and methods: The real-time quantitative polymerase chain reaction (RT-qPCR) was performed to assess the expression levels of circ-PRMT5, miR-188-5p and anti-Hexokinase II (HK2) in HCC tissues and cells. The cell proliferation, migration and glycolysis were determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell migration assay, and indicated kits, respectively. The interaction relationship between miR-188-5p and circ-PRMT5 or HK2 was analyzed by the bioinformatics database, dual-luciferase reporter assay, and RNA immunoprecipitation (RIP) assay. The western blot assay was used to analyze the expression level of HK2. The functional role of circ-PRMT5 in vivo was assessed by a xenograft experiment.Results: Circ-PRMT5 was elevated in HCC tissues and cells than matched control groups. Furthermore, loss-of-functional experiments revealed that the silencing of circ-PRMT5 could repress proliferation, migration, glycolysis in vitro and tumor growth in vivo. Moreover, we also confirmed that overexpression of circ-PRMT5 abolished the effects on HCC cells induced by upregulating miR-188-5p. In addition, overexpression of miR-188-5p could repress the development of HCC. More importantly, HK2 was a target gene of miR-188-5p, and miR-188-5p regulated proliferation, migration, glycolysis of HCC cells by specifically binding to HK2. Mechanistically, circ-PRMT5 could act as a sponge of miR-188-5p to regulate the expression of HK2.Conclusion: In summary, circ-PRMT5 might play a key role in proliferation, migration, glycolysis of HCC cells via miR-188-5p/HK2 axis, which indicated that circ-PRMT5 might be a potential therapeutic target for HCC treatment. (c) 2020 Fundacion Clinica Medica Sur, A.C. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).