环状 RNA hsa_circ_0091579 通过 miR-624/H3F3B 轴促进肝癌细胞的瓦博格效应和恶性转化。
Circular RNA hsa_circ_0091579 facilitates the Warburg effect and malignancy of hepatocellular carcinoma cells via the miR-624/H3F3B axis.
机构信息
Department of Hepatobiliary Surgery, Tengzhou Central People's Hospital of Shandong Province, Tengzhou, Shandong, China.
Department of Medical, Yantai Hospital of Traditional Chinese Medicine, Antai, Shandong, China.
出版信息
Clin Transl Oncol. 2021 Nov;23(11):2280-2292. doi: 10.1007/s12094-021-02627-4. Epub 2021 May 1.
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.
背景
肝细胞癌（HCC）是一种高死亡率的原发性肝癌。据报道，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
通过实时定量聚合酶链反应（qRT-PCR）评估 circ_0091579、microRNA（miR）-624 和 H3 组蛋白家族成员 3B（H3F3B）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）和耗氧量（OCR）。使用商业试剂盒评估三磷酸腺苷（ATP）水平。通过划痕愈合、Transwell 或流式细胞术测定细胞迁移、侵袭和凋亡。通过荧光素酶报告测定和/或 RNA 免疫沉淀（RIP）测定验证 miR-624 与 circ_0091579 或 H3F3B 的关系。通过 Western blot 检测 H3F3B 蛋白水平。
结果
circ_0091579 在 HCC 组织和细胞中上调。circ_0091579 抑制可降低体内异种移植肿瘤生长，并抑制 HCC 细胞的体外 Warburg 效应、迁移、侵袭和诱导凋亡。miR-624 在 HCC 组织和细胞中下调，而 H3F3B 上调。circ_0091579 作为 miR-624 的海绵体，通过吸附 miR-624 调节 H3F3B 的表达。miR-624 抑制剂逆转了 circ_0091579 下调对 HCC 细胞 Warburg 效应和恶性行为的影响。H3F3B 过表达逆转了 miR-624 模拟物对 HCC 细胞 Warburg 效应和恶性行为的抑制作用。
结论
circ_0091579 通过吸附 miR-624 上调 H3F3B，加速 HCC 中的 Warburg 效应和肿瘤生长，为 circ_0091579 参与 HCC 进展提供了证据。
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