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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
MicroRNA-1306-5p Regulates the METTL14-Guided m6A Methylation to Repress Acute Myeloid Leukemia
Jiajia Li1, Yanping Wu1, Meng Wang1
1Department of Hematology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
Abstract:
miRNA and m6A methylation are two key regulators in cancers. However, in acute myeloid leukemia (AML), the relationship of miRNA and m6A methylation remains unclear. The present work is aimed at determining the effect of m6A methylation induced by miRNAs on AML and its underlying mechanism. The expression of METTL14 was detected by qRT-PCR and western blot. The growth of HL-60 cells was analyzed by CCK-8, Transwell assay, and flow cytometry. Tumor-bearing mice were established, and Ki-67 staining assay was used to detect the proliferation in vivo. Dual luciferase reporter system detected the effect of miR-1306-5p on METTL14 luciferase activity. Dot blot analysis detected m6A methylation. We found that METTL14 was upregulated in AML patients and overexpressed METTL14 promoted AML development. Further analysis indicated that METTL14 was directly targeted by miR-1306-5p and overexpressed miR-1306-5p alleviated AML progression. In addition, m6A methylation level regulated by METTL14 could be affected by miR-1306-5p. In conclusion, we found that suppressed miR-1306-5p enhanced AML progression by elevating m6A methylation level via upregulating METTL14. These findings provided basis for the development of new strategies for treating AML.
Insights
MicroRNAs (miRNAs) and m6A methylation are crucial in cancer. In acute myeloid leukemia (AML), suppressed miR-1306-5p promotes cancer progression by increasing m6A methylation via METTL14 upregulation.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- MicroRNAs (miRNAs) and N6-methyladenosine (m6A) methylation are key regulators in cancer.
- The precise relationship between miRNA and m6A methylation in acute myeloid leukemia (AML) remains incompletely understood.
Purpose of the Study:
- To elucidate the effect of m6A methylation induced by miRNAs on AML.
- To investigate the underlying molecular mechanisms connecting miRNA, m6A methylation, and AML progression.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot to assess METTL14 expression.
- Cell proliferation assays (CCK-8, Transwell, flow cytometry) and in vivo tumor models with Ki-67 staining.
- Dual-luciferase reporter assays, dot blot analysis for m6A methylation detection.
Main Results:
- METTL14 was found to be upregulated in AML patients, and its overexpression promoted AML development.
- miR-1306-5p was identified as a direct targeting miRNA of METTL14; its overexpression alleviated AML progression.
- The m6A methylation level, regulated by METTL14, was shown to be influenced by miR-1306-5p.
Conclusions:
- Suppressed miR-1306-5p enhances AML progression by increasing m6A methylation levels through METTL14 upregulation.
- These findings offer a mechanistic basis for developing novel therapeutic strategies for AML.
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