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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
A natural antisense transcript regulates acetylcholinesterase gene expression via epigenetic modification in
Qiliang Xi1, Ning Gao2, Xuejin Zhang1
1State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 320 YueYang Road, Shanghai 200031, PR China.
Abstract:
In recent years, widespread antisense transcripts have been identified systematically in mammalian cells and are known to regulate gene expression, although their functional significance remains largely unknown. Previous work has identified that acetylcholinesterase (AChE) is expressed aberrantly in various malignant tumors and function as a tumor growth suppressor. However, the mechanism of AChE gene regulation in tumors remains unclear. In this study, we show that the AChE antisense RNA (AChE-AS) play an important role in AChE expression regulation. An inverse relationship was identified between AChE-AS and AChE expression in hepatocellular carcinoma and hepatoma cells. The silenced AChE-AS corresponds to elevated expression of AChE. Furthermore, we demonstrated that reduced AChE-AS increased H3K4 methylation and decreased H3K9 methylation in the AChE promoter region. As expected, elevated AChE levels induced by inhibition of AChE-AS enhanced anticarcinogen-induced apoptosis. These observations demonstrated that AChE-AS modulates AChE expression and exerts an anti-apoptotic effect through direct repression of AChE expression in HCC cells. Thus, natural antisense RNA may play an important role in AChE regulation via affecting the epigenetic modification in the AChE promoter region.
Insights
AChE antisense RNA (AChE-AS) regulates acetylcholinesterase (AChE) expression in liver cancer. Silencing AChE-AS increases AChE, promoting apoptosis and tumor suppression via epigenetic changes.
Area of Science:
- Molecular Biology
- Epigenetics
- Cancer Research
Background:
- Antisense transcripts regulate gene expression, but their functions are often unclear.
- Acetylcholinesterase (AChE) acts as a tumor suppressor but its regulation in cancer is not fully understood.
Purpose of the Study:
- To investigate the role of AChE antisense RNA (AChE-AS) in regulating AChE expression in hepatocellular carcinoma (HCC).
- To elucidate the mechanism by which AChE-AS affects AChE expression and tumor cell apoptosis.
Main Methods:
- Analysis of the relationship between AChE-AS and AChE expression in HCC and hepatoma cells.
- Investigation of epigenetic modifications (H3K4 and H3K9 methylation) in the AChE promoter region upon AChE-AS manipulation.
- Assessment of apoptosis levels following inhibition of AChE-AS.
Main Results:
- An inverse correlation was observed between AChE-AS and AChE expression in liver cancer cells.
- Reduced AChE-AS led to increased AChE expression, associated with altered H3K4 and H3K9 methylation at the AChE promoter.
- Elevated AChE levels, induced by AChE-AS inhibition, enhanced apoptosis.
Conclusions:
- AChE-AS plays a critical role in repressing AChE expression in HCC cells.
- AChE-AS modulates AChE expression through epigenetic modifications in the promoter region.
- Natural antisense RNAs like AChE-AS are important regulators of gene expression and may influence tumor suppression.
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