ALYREF promotes the metastasis of nasopharyngeal carcinoma by increasing the stability of NOTCH1 mRNA.
Ya-Nan JinJijin YaoJianchang FuQitao HuangYilin LuoYafei YouWangjian ZhangQian ZhongTianliang XiaLiangping XiaPublished in: Cell death & disease (2024)
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.
Keyphrases
- poor prognosis
- gene expression
- long non coding rna
- cell proliferation
- signaling pathway
- induced apoptosis
- transcription factor
- healthcare
- end stage renal disease
- newly diagnosed
- machine learning
- pi k akt
- binding protein
- social media
- genome wide
- peritoneal dialysis
- patient reported
- artificial intelligence
- cell cycle arrest
- endoplasmic reticulum stress