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METTL3 Mediated MALAT1 m6A Modification Promotes Proliferation and Metastasis in Osteosarcoma Cells
Yuanzhuang Zhang1, Yeqiu Xu1, Guanzhen Qiu1
1Fourth Department of Orthopedic Surgery, Central Hospital Affiliated to Shenyang Medical College, No. 5 South Seven West Road, Tiexi, Shenyang, 110024, Liaoning, P.R. China.
Molecular Biotechnology
|October 28, 2023
Summary
Methyltransferase-like 3 (METTL3) promotes osteosarcoma progression by increasing the stability of Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) via m6A modification. This oncogenic function enhances cell proliferation and migration.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- N6-methyladenosine (m6A) is a crucial RNA modification implicated in various cancers, including osteosarcoma.
- Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) has a partially understood role in osteosarcoma.
- The specific role of methyltransferase-like 3 (METTL3) and its impact on MALAT1 in osteosarcoma remains unclear.
Purpose of the Study:
- To investigate the role of METTL3 in osteosarcoma.
- To explore the relationship between METTL3 and MALAT1 in osteosarcoma.
- To elucidate the m6A modification mechanism of MALAT1 by METTL3 in osteosarcoma.
Main Methods:
- Bioinformatics analysis, immunohistochemistry, western blotting, and RT-qPCR were used to assess METTL3 and MALAT1 expression.
- Cell Counting Kit-8 and Transwell assays evaluated cell proliferation and invasion.
- MeRIP-qPCR and actinomycin D assays investigated m6A modification and RNA stability.
Main Results:
- METTL3 expression was significantly upregulated in osteosarcoma tissues and cell lines.
- METTL3 promoted osteosarcoma cell proliferation and migration.
- METTL3 positively correlated with MALAT1 expression, which was also upregulated. METTL3-mediated m6A modification stabilized MALAT1, enhancing its oncogenic functions.
Conclusions:
- METTL3 functions as an oncogene in osteosarcoma.
- METTL3 promotes osteosarcoma progression by enhancing MALAT1 stability through m6A modification.
- METTL3-METTL3-MALAT1 axis plays a critical role in osteosarcoma development.
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