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Published on: September 25, 2019
Long Noncoding RNA TFAP2A-AS1 Suppressed Hepatitis B Virus Replication by Modulating miR-933/HDAC11
Yu Cheng1, Weiwu Shi2, Xudong Cui1
1Department of Infectious Disease, The Fourth Hospital of Harbin Medical University, Harbin, 150001 Heilongjiang, China.
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.
Insights
Long noncoding RNA TFAP2A-AS1 is downregulated in hepatocellular carcinoma (HCC) and suppresses hepatitis B virus (HBV) replication. Upregulation of TFAP2A-AS1 inhibits HBV DNA, HBeAg, and HBsAg expression, suggesting its therapeutic potential.
Area of Science:
- Molecular Biology
- Hepatology
- Oncology
Background:
- Long noncoding RNAs (lncRNAs) are implicated in various cancers, including hepatocellular carcinoma (HCC).
- Hepatitis B virus (HBV) infection is a major cause of HCC, and its molecular mechanisms are not fully understood.
- The role of specific lncRNAs, such as TFAP2A-AS1, in HBV-associated HCC requires further investigation.
Purpose of the Study:
- To investigate the role of lncRNA TFAP2A-AS1 in hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection.
- To elucidate the regulatory mechanism of TFAP2A-AS1 in HBV replication and HCC progression.
Main Methods:
- Quantitative reverse transcription PCR (qRT-PCR) to assess TFAP2A-AS1 and miR-933 levels.
- Luciferase reporter gene assays to determine interactions between TFAP2A-AS1, miR-933, and HDAC11.
- Cell proliferation assays (CCK-8) and HBV DNA replication detection (RT-qPCR).
Main Results:
- TFAP2A-AS1 was downregulated, while miR-933 was upregulated in HCC cell lines and HBV-infected HCC samples.
- TFAP2A-AS1 functioned as a molecular sponge for miR-933, and HDAC11 was a direct target of miR-933.
- Overexpression of TFAP2A-AS1 suppressed cell growth, HBV DNA replication, HBeAg, and HBsAg expression, whereas miR-933 promoted these processes.
Conclusions:
- TFAP2A-AS1 plays a critical role in regulating HBeAg and HBsAg expression and HBV replication.
- TFAP2A-AS1 may serve as a potential therapeutic target for HBV infection-related HCC.
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