长链非编码 RNA TFAP2A-AS1 通过调控 miR-933/HDAC11 抑制乙型肝炎病毒复制。
Long Noncoding RNA TFAP2A-AS1 Suppressed Hepatitis B Virus Replication by Modulating miR-933/HDAC11.
机构信息
Department of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang, China.
Department of integrated internal medicine, Shanghai Donghai Senior Nursing Hospital, Shanghai, China.
出版信息
Dis Markers. 2022 Apr 18;2022:7733390. doi: 10.1155/2022/7733390. eCollection 2022.
OBJECTIVE
Studies have shown that long noncoding RNAs (lncRNAs) play crucial roles in multiple tumor types and regulate various biological processes. The present study tried to study lncRNA TFAP2A-AS1 in HBV infection hepatocellular carcinoma.
METHODS
The level of TFAP2A-AS1 and miR-933 in HCC cell and samples were detected by qRT-PCR assay. Luciferase reporter gene assay was carried out to study the mechanism of TFAP2A-AS1 and miR-933. Cell proliferation was measured by CCK-8 assay. HBV DNA replication was detected by RT-qPCR.
RESULTS
We firstly demonstrated that TFAP2A-AS1 was downregulated in HCC cell lines and HBV-infected HCC samples compared with nontumor tissues. However, miR-933 was upregulated in HCC cell lines and HBV-infected HCC samples compared with nontumor tissues, and miR-933 was negatively associated with the expression of TFAP2A-AS1 in HBV-correlated HCC samples. TFAP2A-AS1 and HDAC11 expression was decreased and miR-933 was upregulated in the HBV-infected cell HepG2.2.15. TFAP2A-AS1 acted as a sponge for miR-933 and HDAC11 was one direct target gene for miR-933. Overexpression of TFAP2A-AS1 suppressed cell growth, HBV DNA replication, HbeAg, and HbsAg expression, while knockdown of TFAP2A-AS1 enhanced cell proliferation, HBV DNA replication, HbeAg, and HbsAg expression in HepG2.2.15 cell. In addition, ectopic expression of miR-933 promoted cell growth, HBV DNA replication, HbeAg, and HbsAg expression in HepG2.2.15 cell. TFAP2A-AS1 suppressed HBV replication and infection through regulating HDAC11.
CONCLUSION
These data demonstrated that TFAP2A-AS1 acted crucial roles in the modulation of HbeAg and HbsAg expression and HBV replication and may be one potential target for HBV infection treatment.
目的
研究表明，长链非编码 RNA（lncRNA）在多种肿瘤类型中发挥关键作用，并调节各种生物学过程。本研究试图研究乙型肝炎病毒（HBV）感染肝细胞癌中的 lncRNA TFAP2A-AS1。
方法
通过 qRT-PCR 检测 HCC 细胞和样本中 TFAP2A-AS1 和 miR-933 的水平。通过荧光素酶报告基因实验研究 TFAP2A-AS1 和 miR-933 的作用机制。通过 CCK-8 法检测细胞增殖。通过 RT-qPCR 检测 HBV DNA 复制。
结果
我们首先证明，与非肿瘤组织相比，TFAP2A-AS1 在 HCC 细胞系和 HBV 感染的 HCC 样本中下调，而 miR-933 在 HCC 细胞系和 HBV 感染的 HCC 样本中上调，并且 miR-933 与 HBV 相关 HCC 样本中 TFAP2A-AS1 的表达呈负相关。在 HBV 感染的 HepG2.2.15 细胞中，TFAP2A-AS1 和 HDAC11 的表达降低，miR-933 上调。TFAP2A-AS1 作为 miR-933 的海绵，HDAC11 是 miR-933 的一个直接靶基因。过表达 TFAP2A-AS1 抑制细胞生长、HBV DNA 复制、HbeAg 和 HbsAg 表达，而敲低 TFAP2A-AS1 增强 HepG2.2.15 细胞的增殖、HBV DNA 复制、HbeAg 和 HbsAg 表达。此外，miR-933 的过表达促进了 HepG2.2.15 细胞的生长、HBV DNA 复制、HbeAg 和 HbsAg 表达。TFAP2A-AS1 通过调节 HDAC11 抑制 HBV 复制和感染。
结论
这些数据表明，TFAP2A-AS1 在调节 HbeAg 和 HbsAg 表达和 HBV 复制中发挥重要作用，可能是 HBV 感染治疗的潜在靶点。
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