Circular RNA hsa_circ_0091579 facilitates the Warburg effect and malignancy of hepatocellular carcinoma cells via the miR-624/H3F3B axis
Circular RNA hsa_circ_0091579 facilitates the Warburg effect and malignancy of hepatocellular carcinoma cells via the miR-624/H3F3B axis
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DOI：
10.1007/s12094-021-02627-4
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发表时间：
2021-05-01
影响因子：
3.4
通讯作者：
Zhang, Y.
中科院分区：
文献类型：
--
作者：
Chen, Y.;Song, S.;Zhang, Y.
背景肝细胞癌（HCC）是一种死亡率高的原发性肝癌。已有报道环状RNA hsa_circ_0091579（circ_0091579）参与HCC进展。然而，circ_0091579调节HCC进展的分子机制尚不清楚。方法采用实时荧光定量聚合酶链反应（qRT-PCR）检测circ_0091579、microRNA（miR）-624和H3组蛋白家族成员3B（H3 F3 B）mRNA的表达。使用细胞外通量分析仪分析HCC细胞的细胞外酸化率（ECAR）和耗氧率（OCR）。使用市售试剂盒评价三磷酸腺苷（ATP）水平。通过伤口愈合、transwell或流式细胞术分析评估细胞迁移、侵袭和凋亡。使用荧光素酶报告基因测定和/或RNA免疫沉淀（RIP）测定验证miR-624与circ_0091579或H3 F3 B之间的关系。Western blotting检测H3 F3 B蛋白水平。结果Circ_0091579在肝癌组织和细胞中表达上调。Circ_0091579抑制在体内减少异种移植肿瘤生长，并在体外抑制瓦尔堡效应、迁移、侵袭和诱导HCC细胞凋亡。miR-624在HCC组织和细胞中下调，而H3 F3 B在HCC组织和细胞中上调。Circ_0091579充当miR-624海绵并通过吸附miR-624调节H3 F3 B表达。miR-624抑制剂逆转了circ_0091579下调介导的对HCC细胞的瓦尔堡效应和恶性行为的影响。H3 F3 B过表达逆转了miR-624模拟物对肝癌细胞的瓦尔堡效应和恶性程度的抑制作用。结论Circ_0091579通过吸附miR-624上调H3 F3 B，促进肝癌细胞的瓦尔堡效应和肿瘤生长，为Circ_0091579参与肝癌的发生发展提供了证据。
Background Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. It has been reported that circular RNA hsa_circ_0091579 (circ_0091579) is involved in HCC progression. Nevertheless, the molecular mechanism by which circ_0091579 modulates HCC advancement is indistinct. Methods The expression of circ_0091579, microRNA (miR)-624, and H3 histone family member 3B (H3F3B) mRNA was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of HCC cells were analyzed using an extracellular flux analyzer. Adenosine triphosphate (ATP) level was evaluated using a commercial kit. Cell migration, invasion, and apoptosis were assessed by wound-healing, transwell, or flow cytometry assay. The relationship between miR-624 and circ_0091579 or H3F3B was verified using luciferase reporter assay and/or RNA immunoprecipitation (RIP) assay. H3F3B protein level was detected by western blotting. Results Circ_0091579 was upregulated in HCC tissues and cells. Circ_0091579 inhibition decreased xenograft tumor growth in vivo and repressed Warburg effect, migration, invasion, and induced apoptosis of HCC cells in vitro. MiR-624 was downregulated, while H3F3B was upregulated in HCC tissues and cells. Circ_0091579 acted as a miR-624 sponge and regulated H3F3B expression by adsorbing miR-624. MiR-624 inhibitor reversed circ_0091579 downregulation-mediated effects on the Warburg effect and malignant behaviors of HCC cells. H3F3B overexpression reversed the repressive impact of miR-624 mimic on the Warburg effect and malignancy of HCC cells. Conclusions Circ_0091579 accelerated Warburg effect and tumor growth via upregulating H3F3B via adsorbing miR-624 in HCC, providing evidence to support the involvement of circ_0091579 in the progression of HCC.