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MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer
Jun Wei1, Zijian Wang1, Zhixiang Wang1
1Department of Gastroenterology, Yancheng Affiliated Hospital of Southeast University, Yancheng 224000, China.
Abstract:
Gastric cancer is one of the most lethal malignancies worldwide. The aberrant expression of microRNA-31 (miR-31) has been reported in gastric cancer; however, its regulation mechanisms are still unclear. Here, we confirmed that miR-31 expression was significantly decreased in gastric cancer tissue and cell lines. Ectopic expression of miR-31 potentially suppresses proliferation and induced early apoptosis in gastric cancer cells. Furthermore, miR-31 expression was regulated as a result of epigenetic mechanisms. The downregulation of miR-31 was associated with promoter DNA methylation status in gastric cancer and cell lines. Moreover, we found that HDAC2 was the direct target of miR-31 by binding to 3'-UTR from the results of luciferase reporter assays, qRT-PCR, and western blotting. HDAC2 played an activation role in tumor growth, whose expression is upregulated and inversely associated with miR-31 levels. All the results suggested that miR-31 function as a crucial tumor suppressor was regulated by epigenetic mechanisms in gastric cancer. We found an epigenetic pathway loop, DNA methylation-miRNA expression-target gene-tumor progression in gastric cancer, and also provided implications for molecular diagnosis and therapeutics of gastric malignancies by detecting miR-31 as a potential target.
Insights
MicroRNA-31 (miR-31) is downregulated in gastric cancer due to DNA methylation. Restoring miR-31 suppresses tumor growth by targeting HDAC2, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Gastric cancer is a leading cause of cancer mortality globally.
- Aberrant microRNA-31 (miR-31) expression is observed in gastric cancer, but its regulatory mechanisms remain unclear.
- Understanding miR-31 regulation is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the regulatory mechanisms of miR-31 in gastric cancer.
- To determine the functional role of miR-31 in gastric cancer progression.
- To identify potential therapeutic targets for gastric cancer treatment.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blotting to assess gene and protein expression.
- Luciferase reporter assays to confirm direct targeting of HDAC2 by miR-31.
- Analysis of DNA methylation status in gastric cancer tissues and cell lines.
Main Results:
- miR-31 expression was significantly decreased in gastric cancer tissues and cell lines.
- Ectopic miR-31 expression inhibited gastric cancer cell proliferation and induced apoptosis.
- Downregulation of miR-31 was linked to promoter DNA methylation, indicating epigenetic regulation.
- HDAC2 was identified as a direct target of miR-31, with its expression inversely correlated with miR-31 levels.
Conclusions:
- miR-31 acts as a tumor suppressor in gastric cancer, with its expression epigenetically regulated by DNA methylation.
- An epigenetic pathway involving DNA methylation, miR-31, and HDAC2 contributes to gastric cancer progression.
- miR-31 holds potential as a biomarker for molecular diagnosis and a therapeutic target for gastric cancer.
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