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Updated: Jun 8, 2025
A Method for Measuring RNA N6-methyladenosine Modifications in Cells and Tissues
Published on: December 5, 2016
METTL14 Induced N6-Methyladenosine Modification of FOXP4 mRNA in HBV-HCC
Tian-Tian Wang1, Yi-Mei Ji1, Qian Zhang1
1Department of Endoscopy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China.
Abstract:
Chronic hepatitis B virus infections are a significant cause of liver cirrhosis and cancer. Our research reveals that HBV infection leads to a marked increase in m6A modification of Foxp4 mRNA, resulting in enhanced stability of the mRNA and a subsequent increase in Foxp4 mRNA levels. Analysis of biopsy samples from chronic HBV patients demonstrated consistent upregulation of m6A-modified Foxp4 mRNA levels alongside increased Foxp4 mRNA levels. Functionally, Foxp4 was found to promote proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells in laboratory settings. Additionally, HBV gene expression was shown to activate the PI3K/AKT pathway by modulating Foxp4 mRNA stability in HCC cells. This study provides valuable insights into the underlying mechanisms of HBV infection and its potential implications for cancer development.
Insights
Hepatitis B virus (HBV) infection increases m6A modification of Foxp4 mRNA, boosting its levels and promoting liver cancer cell growth. This mechanism involves the PI3K/AKT pathway, offering insights into HBV-related cancer development.
Area of Science:
- Hepatology
- Oncology
- Molecular Biology
Background:
- Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma (HCC).
- The molecular mechanisms linking HBV infection to liver cancer progression require further elucidation.
Purpose of the Study:
- To investigate the role of m6A modification of Forkhead box protein 4 (Foxp4) mRNA in HBV-related liver cancer.
- To explore the functional impact of altered Foxp4 expression on HCC cell behavior and signaling pathways.
Main Methods:
- Analysis of m6A modification and mRNA levels of Foxp4 in HBV-infected cells and patient biopsy samples.
- In vitro functional assays (proliferation, migration, invasion) using HCC cells.
- Investigation of the PI3K/AKT pathway activation in response to HBV gene expression and Foxp4 modulation.
Main Results:
- HBV infection significantly increases m6A modification and stability of Foxp4 mRNA, leading to elevated Foxp4 mRNA levels.
- Foxp4 promotes proliferation, migration, and invasion of HCC cells.
- HBV gene expression activates the PI3K/AKT pathway by modulating Foxp4 mRNA stability.
Conclusions:
- Increased m6A-modified Foxp4 mRNA is a key mechanism in HBV-associated liver cancer.
- Foxp4 acts as an oncogene in HCC, driven by HBV infection.
- Targeting the Foxp4/PI3K/AKT axis may offer therapeutic strategies for HBV-related HCC.
