METTL16 promotes osteosarcoma progression by inducing m6A methylation of the UBE3A and Notch signaling pathway
Year: 2025
Type: article
Abstract: N6-methyladenosine (m 6 A) methylation plays a key role in osteosarcoma (OS) progression. This study aimed to elucidate the function and mechanism of methyltransferase 16 (METTL16), an m 6 A methyltransferase, in OS progression. Bioinformatics analysis with quantitative reverse-transcription polymerase chain reaction (qRT-PCR) revealed high METTL16 expression in OS. After performing cell functional experiments, METTL16 silencing was shown to decrease the proliferation, migration, and invasion of OS cells. Using qRT-PCR, methylated RNA immunoprecipitation quantitative polymerase chain reaction (MeRIP-qPCR), Western blotting, luciferase, RNA binding protein immunoprecipitation (RIP), and RNA stability assays, METTL16 induced the m 6 A methylation of ubiquitin protein ligase E3A (UBE3A) to promote UBE3A expression and mRNA stability in OS cells in a fragile X messenger ribonucleoprotein 1 (FMR1)-dependent manner. Moreover, in vitro and in vivo results showed that UBE3A activated the Notch signaling pathway, thereby promoting OS cell malignancy. METTL16 knockdown partly reversed the oncogenic role of UBE3A in OS cells. METTL16 acts as a tumor promotor in OS progression by modulating UBE3A expression via m 6 A methylation to activate the Notch signaling pathway. The findings highlight the therapeutic potential of disrupting the METTL16–UBE3A–Notch pathway axis in OS.
Authors: Yanlin Tan, Jun Gao
Institutions: Wuhan Third Hospital, Hubei Zhongshan Hospital
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,100
OpenAlex ID: W4415005152