环状ATP5H通过调控miR-138-5p/轴诱导乙型肝炎病毒复制和表达。
Circ-ATP5H Induces Hepatitis B Virus Replication and Expression by Regulating miR-138-5p/ Axis.
作者信息
Jiang Wenxiu, Wang Lili, Zhang Yajuan, Li Hongliang
机构信息
Department of Infectious Diseases, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Danyang City, Jiangsu Province, People's Republic of China.
Department of Clinical Research, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing City, Jiangsu Province, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Nov 2;12:11031-11040. doi: 10.2147/CMAR.S272983. eCollection 2020.
BACKGROUND
Circular RNAs (circRNAs) play an important regulatory role in various cancers, including hepatocellular carcinoma (HCC). This study aimed to investigate the function of hsa_circ_0006942 (circ-ATP5H) in hepatitis B virus (HBV)-associated HCC and its underlying mechanism.
METHODS
The levels of circ-ATP5H, miR-138-5p and tumor necrosis factor alpha-induced protein 3 () were determined using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The copies of HBV DNA were examined using qRT-PCR. The levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were detected via enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was used to analyze the interactions among circ-ATP5H, miR-138-5p and .
RESULTS
Circ-ATP5H and levels were increased, while miR-138-5p level was reduced in HBV-positive HCC tissues and cells. Knockdown of circ-ATP5H hindered HBV DNA replication and decreased HBsAg and HBeAg levels in HBV-infected cells. Circ-ATP5H silencing suppressed HBV replication and expression by regulating miR-138-5p. Moreover, miR-138-5p blocked HBV replication and expression via targeting . Furthermore, circ-ATP5H up-regulated via absorbing miR-138-5p.
CONCLUSION
Circ-ATP5H promoted HBV replication and expression through modulating miR-138-5p/ axis, suggesting a new biomarker for HBV-related HCC treatment.
背景
环状RNA（circRNAs）在包括肝细胞癌（HCC）在内的多种癌症中发挥重要的调节作用。本研究旨在探讨hsa_circ_0006942（circ-ATP5H）在乙型肝炎病毒（HBV）相关HCC中的功能及其潜在机制。
方法
采用定量实时聚合酶链反应（qRT-PCR）或蛋白质免疫印迹法检测circ-ATP5H、miR-138-5p和肿瘤坏死因子α诱导蛋白3（）的水平。采用qRT-PCR检测HBV DNA拷贝数。通过酶联免疫吸附测定（ELISA）检测乙型肝炎表面抗原（HBsAg）和乙型肝炎e抗原（HBeAg）水平。采用双荧光素酶报告基因检测法分析circ-ATP5H、miR-138-5p和之间的相互作用。
结果
HBV阳性HCC组织和细胞中circ-ATP5H和水平升高，而miR-138-5p水平降低。敲低circ-ATP5H可抑制HBV感染细胞中的HBV DNA复制，并降低HBsAg和HBeAg水平。circ-ATP5H沉默通过调节miR-138-5p抑制HBV复制和表达。此外，miR-138-5p通过靶向阻断HBV复制和表达。此外，circ-ATP5H通过吸收miR-138-5p上调。
结论
circ-ATP5H通过调节miR-138-5p/轴促进HBV复制和表达，提示其可能成为HBV相关HCC治疗的新生物标志物。
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