ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion
© 2024. The Author(s)..
Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Cell death discovery - 10(2024), 1 vom: 24. Feb., Seite 97 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Meng, Qingbo [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
|---|
| Anmerkungen: |
Date Revised 27.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.1038/s41420-024-01862-2 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368921727 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368921727 | ||
| 003 | DE-627 | ||
| 005 | 20240229164833.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41420-024-01862-2 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1309.xml |
| 035 | |a (DE-627)NLM368921727 | ||
| 035 | |a (NLM)38402198 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Meng, Qingbo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ALYREF-JunD-SLC7A5 axis promotes pancreatic ductal adenocarcinoma progression through epitranscriptome-metabolism reprogramming and immune evasion |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 27.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Pancreatic ductal adenocarcinoma (PDAC) is a kind of tumor lacking nutrients due to its poor vascularity and desmoplasia. Recent studies have shown that cancer cells might achieve growth advantage through epitranscriptome reprogramming. However, the role of m5C in PDAC was not fully understood. We found that Aly/REF export factor (ALYREF), a reader of m5C modification, was overexpressed in PDAC, and associated with bad prognosis. In addition, the ALYREF expression was negatively related to CD8+ T cells infiltration in clinical samples. ALYREF knockdown decreased tumor growth in vivo partly dependent of immunity. ALYREF silencing decreased SLC7A5 expression and subsequently inactivated mTORC1 pathway, resulting in decreased tumor proliferation. Mechanically, ALYREF specifically recognized m5C sites in JunD mRNA, maintained the stabilization of JunD mRNA and subsequently upregulated transcription of SLC7A5. Since SLC7A5 was a key transporter of large neutral amino acids (LNAAs), overexpression of SLC7A5 on tumor cells depleted amino acid in microenvironment and restricted CD8+ T cells function. Moreover, ALYREF-JunD-SLC7A5 axis was overexpressed and negatively related with survival through TMA assays. In conclusion, this research revealed the relationship between m5C modification, amino acid transportation and immune microenvironment. ALYREF might be a novel target for PDAC metabolic vulnerability and immune surveillance | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Xie, Yuting |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Kang |e verfasserin |4 aut | |
| 700 | 1 | |a He, Lihong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Hongkun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Tingbo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Cell death discovery |d 2015 |g 10(2024), 1 vom: 24. Feb., Seite 97 |w (DE-627)NLM251897435 |x 2058-7716 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2024 |g number:1 |g day:24 |g month:02 |g pages:97 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41420-024-01862-2 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2024 |e 1 |b 24 |c 02 |h 97 | ||