NR2F1-AS1/miR-140/HK2 Axis Regulates Hypoxia-Induced Glycolysis and Migration in Hepatocellular Carcinoma.
NR2F1-AS1/miR-140/HK2 Axis Regulates Hypoxia-Induced Glycolysis and Migration in Hepatocellular Carcinoma.
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DOI：
10.2147/cmar.s266797
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发表时间：
2021
影响因子：
3.3
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Li X;Li Y;Bai S;Zhang J;Liu Z;Yang J
低氧是肝细胞癌进展的一个重要特征。长非编码核受体亚家族2组F成员1反义RNA 1(NR2F1-AS1)在肝细胞癌中表达异常。然而，N2RF1-AS1在低氧诱导的糖酵解和迁移中的作用和机制尚不清楚。采集40例肝癌患者的肿瘤组织及癌旁组织标本。对肝癌细胞进行低氧处理。用定量逆转录聚合酶链式反应或Western印迹法检测NR2F1-AS1、microRNA(MiR)-140和己糖激酶2(HK2)的表达水平。糖酵解通过葡萄糖摄取、乳酸生成和三磷酸腺苷(ATP)水平进行分析。Transwell法分析细胞迁移情况。通过双荧光素酶报告实验和RNA免疫沉淀分析靶结合。NR2F1-AS1在肝细胞癌组织和细胞中表达增强。NR2F1-AS1高表达提示总生存率较低。沉默NR2F1-AS1抑制低氧诱导的肝癌细胞糖酵解和迁移。NR2F1-AS1可能通过调节miR-140来调节HK2的表达。MIR-140下调或HK2上调可减轻NR2F1-AS1沉默对低氧诱导的肝癌细胞糖酵解和迁移的影响。NR2F1-AS1基因敲除通过增加miR-140和降低HK2来抑制低氧诱导的肝癌细胞糖酵解和迁移。
Hypoxia is an important feature for the progression of hepatocellular carcinoma (HCC). Long noncoding RNA nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) is dysregulated in HCC. However, the role and mechanism of N2RF1-AS1 in hypoxia-induced glycolysis and migration remain unclear. Tumor tissues and adjacent samples were harvested from 40 HCC patients. HCC cells were treated by hypoxia. The levels of NR2F1-AS1, microRNA (miR)-140, and hexokinase 2 (HK2) were examined via quantitative reverse transcription polymerase chain reaction or Western blot. Glycolysis was analyzed via glucose uptake, lactate production, and adenosine triphosphate (ATP) levels. Cell migration was analyzed via transwell assay. The target association was analyzed via dual-luciferase reporter assay and RNA immunoprecipitation. NR2F1-AS1 level was enhanced in HCC tissues and cells. High expression of NR2F1-AS1 indicated poor overall survival. Silence of NR2F1-AS1 repressed hypoxia-induced glycolysis and migration in HCC cells. NR2F1-AS1 could regulate HK2 expression by modulating miR-140. miR-140 down-regulation or HK2 up-regulation mitigated the influence of NR2F1-AS1 silence on hypoxia-induced glycolysis and migration in HCC cells. NR2F1-AS1 knockdown restrained hypoxia-induced glycolysis and migration in HCC cells via increasing miR-140 and decreasing HK2.