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ALYREF promotes the metastasis of nasopharyngeal carcinoma by increasing the stability of NOTCH1 mRNA.
- Source :
-
Cell death & disease [Cell Death Dis] 2024 Aug 08; Vol. 15 (8), pp. 578. Date of Electronic Publication: 2024 Aug 08. - Publication Year :
- 2024
-
Abstract
- Approximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Cell Line, Tumor
Animals
Gene Expression Regulation, Neoplastic
Mice, Nude
Male
Female
Mice
Signal Transduction
Mice, Inbred BALB C
Up-Regulation genetics
Carcinoma metabolism
Carcinoma genetics
Carcinoma pathology
Middle Aged
Receptor, Notch1 metabolism
Receptor, Notch1 genetics
Nasopharyngeal Carcinoma genetics
Nasopharyngeal Carcinoma pathology
Nasopharyngeal Carcinoma metabolism
Nasopharyngeal Neoplasms genetics
Nasopharyngeal Neoplasms pathology
Nasopharyngeal Neoplasms metabolism
RNA, Messenger metabolism
RNA, Messenger genetics
RNA Stability
Neoplasm Metastasis
Subjects
Details
- Language :
- English
- ISSN :
- 2041-4889
- Volume :
- 15
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Cell death & disease
- Publication Type :
- Academic Journal
- Accession number :
- 39117671
- Full Text :
- https://doi.org/10.1038/s41419-024-06959-1