Circ-PRMT5 enhances the proliferation, migration and glycolysis of hepatoma cells by targeting miR-188-5p/HK2 axis

被引:51
作者
Ding, Zhenghua [1 ]
Guo, Li [1 ]
Deng, Zhongming [1 ]
Li, Peng [1 ]
机构
[1] Hubei Univ Med, Affiliated Hosp, Xiangyang Peoples Hosp 1, Dept Gen Surg, 15 Jiefang Rd, Xiangyang 4410001, Hubbei, Peoples R China
关键词
circRNA; circ-PRMT5; miR-188-5p; HK2; HCC; CANCER; METASTASIS;
D O I
10.1016/j.aohep.2020.01.002
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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/).
引用
收藏
页码:269 / 279
页数:11
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