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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The p53/miR-34a/SIRT1 Positive Feedback Loop in Quercetin-Induced Apoptosis
Guohua Lou1, Yanning Liu, Shanshan Wu
1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University. Collaborative Innovation Centre for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China.
Background:
The anti-tumor effects of quercetin have been reported, but the underlying molecular mechanisms remain to be elucidated. The aim of present study was to explore the role of miRNA in the anticancer effects of quercetin.
Methods:
The differential miRNAs expression between the HepG2 and Huh7 cells treated by quercetin were detected by microarray. The xCELLigence, Flow cytometry, RT-PCR and Western blot were used to analyze the cell proliferation, cell apoptosis, cell cycle arrest, anti-tumor genes, and protein expression.
Results:
miR-34a was up-regulated in HepG2 cells treated by quercetin exhibiting wild-type p53. When inhibiting the miR-34a, the sensitivity of the cells to quercetin decreased and the expression of the SIRT1 was up-regulated, but the acetylation of p53 and the expression of some genes related to p53 down-regulated.
Conclusion:
miR-34a plays an important role in the anti-tumor effects of querctin in HCC, miR-34a may be a tiemolecule between the p53 and SIRT1 and is composed of a p53/miR-34a/SIRT1 signal feedback loop, which could enhance apoptosis signal and significantly promote cell apoptosis.
Insights
Quercetin
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Quercetin exhibits anti-tumor properties, but its molecular mechanisms require further investigation.
- Understanding the role of microRNAs (miRNAs) in quercetin's anticancer effects is crucial.
Purpose of the Study:
- To investigate the role of miRNA in mediating the anticancer effects of quercetin.
- To elucidate the molecular pathways involved in quercetin's anti-tumor activity.
Main Methods:
- Microarray analysis to detect differential miRNA expression in HepG2 and Huh7 cells treated with quercetin.
- xCELLigence, flow cytometry, RT-PCR, and Western blot assays to assess cell proliferation, apoptosis, cell cycle, and gene/protein expression.
Main Results:
- miR-34a was upregulated in quercetin-treated HepG2 cells with wild-type p53.
- Inhibiting miR-34a reduced quercetin sensitivity, increased SIRT1 expression, and decreased p53 acetylation and p53-related gene expression.
Conclusions:
- miR-34a is a key mediator of quercetin's anti-tumor effects in hepatocellular carcinoma (HCC).
- A p53/miR-34a/SIRT1 feedback loop enhances apoptosis signaling, promoting cell death in HCC.
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