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METTL14-Mediated RPL13A Expression Regulates Apoptosis and Invasion of Osteosarcoma via the PTEN/PI3K/AKT Signaling
Zilong Chen1, Yanqi Pan1, Yuhang Wei2
1Inner Mongolia Medical University, Hohhot, China.
Summary
Methyltransferase-like 14 (METTL14) regulates osteosarcoma (OS) by modifying ribosomal protein L13a (RPL13a). METTL14-mediated RPL13a m6A modification impacts OS cell behavior via the PTEN/PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Osteosarcoma (OS) is an aggressive bone tumor with poorly understood molecular drivers.
- Ribosomal protein L13a (RPL13a) and methyltransferase-like 14 (METTL14) are implicated in tumorigenesis.
- The PTEN/PI3K/AKT pathway is a known regulator of OS progression.
Purpose of the Study:
- To elucidate the regulatory interactions between METTL14, RPL13a, and the PTEN/PI3K/AKT pathway in OS.
- To confirm METTL14's role in mediating RPL13a N6-methyladenosine (m6A) modification.
- To assess the impact of this interplay on OS cell proliferation, apoptosis, migration, and invasion.
Main Methods:
- Quantitative analysis of METTL14, RPL13a, and m6A levels in OS cell lines and normal osteoblasts.
- Establishment of knockdown (si-RPL13a) and overexpression (METTL14, PTEN) models.
- N6-methyladenosine-specific RNA immunoprecipitation followed by qPCR (M6A-RIP-qPCR) and MeRIP assays.
- Functional assays (CCK-8, flow cytometry, wound healing, Transwell) and molecular analyses (RT-qPCR, Western blotting).
Main Results:
- METTL14 and RPL13a were significantly upregulated in OS cells compared to normal cells.
- METTL14 overexpression increased RPL13a m6A modification, while RPL13a knockdown reduced RPL13a mRNA levels.
- RPL13a knockdown promoted apoptosis and inhibited proliferation, migration, and invasion, partly via PTEN downregulation and PI3K/AKT activation.
- METTL14 overexpression modulated RPL13a/PTEN levels and PI3K/AKT activity, effects dependent on RPL13a status.
Conclusions:
- METTL14 mediates m6A modification of RPL13a mRNA in osteosarcoma.
- RPL13a downregulation, influenced by METTL14, affects PTEN expression and PTEN/PI3K/AKT signaling.
- This pathway modulation contributes to suppressed osteosarcoma cell proliferation, migration, and invasion, alongside enhanced apoptosis.
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