Abstract
Background
As one of the most ubiquitous types of posttranscriptional modification, N6-methyladenosine (m6A) is extensively implicated in almost all types of cancers, including osteosarcoma. Our previous research partially uncovered the role of Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) in osteosarcoma. However, the relationships between methyltransferase-like 3 (METTL3) and noncoding RNAs modified by METTL3, especially MALAT1, in osteosarcoma remain obscure.
Methods
The expression of METTL3 in osteosarcoma was evaluated by online bioinformatics analysis, immunohistochemical (IHC) staining, western blotting (WB), and reverse transcription–quantitative PCR (RT‒qPCR). Cell Counting Kit 8 (CCK-8) and Transwell assays were used to evaluate the cell proliferation and invasion abilities. The expression of MALAT1 in osteosarcoma was evaluated by online bioinformatics analysis and RT‒qPCR analysis. m6A methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) was used to detect m6A modification changes in MALAT1. An actinomycin D assay was used to study changes in the stability of MALAT1.
Results
METTL3 was upregulated in osteosarcoma tissues and cell lines. Functionally, METTL3 promoted the proliferation and migration of osteosarcoma cells. Moreover, a clear positive correlation was found between METTL3 and MALAT1 expression, and MALAT1 was upregulated in osteosarcoma tissues and cells. Mechanistically, the presence of m6A modification sites in MALAT1 and METTL3-mediated m6A modification increased the stability of MALAT1 in osteosarcoma cells and promoted their proliferation and migration.
Conclusion
In this study, it was concluded that in osteosarcoma cells, METTL3, acting as an oncogene, promoted m6A modification of MALAT1, increased the stability of MALAT, and enhanced MALAT1-mediated oncogenic function.
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Data Availability
All the data involved in this study are listed.
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YZ, YX and GQ were responsible for the performance of the experiments; YZ was responsible for the manuscript writing, figure completion and revision of the research. YL, YB, JL and TW were responsible for statistical analysis of the data. YW was mainly responsible for the scientific research and study design.
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The Medical Ethics Committee of Central Hospital Affiliated with Shenyang Medical College approved this study (approval number: 2019DEC12-4), and all patients provided written informed consent.
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Zhang, Y., Xu, Y., Qiu, G. et al. METTL3 Mediated MALAT1 m6A Modification Promotes Proliferation and Metastasis in Osteosarcoma Cells. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00953-2
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DOI: https://doi.org/10.1007/s12033-023-00953-2