LncRNA FOXD1-AS1 regulates pancreatic cancer stem cell properties and 5-FU resistance by regulating the miR-570-3p/SPP1 axis as a ceRNA
© 2023. The Author(s)..
Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
Cancer cell international - 24(2024), 1 vom: 02. Jan., Seite 4 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ouyang, Liu [VerfasserIn] |
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| Links: |
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| Themen: |
Cancer stem cell |
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| Anmerkungen: |
Date Revised 06.01.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s12935-023-03181-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM366577565 |
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| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Cancer stem cells (CSCs) play a pivotal role in the pathogenesis of human cancers. Previous studies have highlighted the role of long non-coding RNA (lncRNA) in modulating the stemness of CSCs. In our investigation, we identified an upregulation of lncRNA FOXD1-AS1 in CSCs. The enforced expression of lncRNA FOXD1-AS1 promotes tumorigenesis and self-renewal in pancreatic cancer CSCs. Conversely, the knockdown of lncRNA FOXD1-AS1 inhibits tumorigenesis and self-renewal in pancreatic cancer CSCs. Furthermore, our findings reveal that lncRNA FOXD1-AS1 enhances self-renewal and tumorigenesis in pancreatic cancer CSCs by up-regulating osteopontin/secreted phosphoprotein 1(SPP1) and acting as a ceRNA to sponge miR-570-3p in pancreatic cancer (PC) CSCs. Additionally, lncRNA FOXD1-AS1 depleted pancreatic cancer cells exhibit heightened sensitivity to 5-FU-indued cell growth inhibition and apoptosis. Analysis of patient-derived xenografts (PDX) indicates that a low level of lncRNA FOXD1-AS1 may serve as a predictor of 5-FU benefits in PC patients. Moreover, the introduction of SPP1 can reverse the sensitivity of lncRNA FOXD1-AS1-knockdown PC cells to 5-FU-induced cell apoptosis. Importantly, molecular studies have indicated that the elevated levels of lncRNAFOXD1-AS1 in PC are facilitated through METTL3 and YTHDF1-dependent m6A methylation. In summary, our results underscore the critical functions of lncRNA FOXD1-AS1 in the self-renewal and tumorigenesis of pancreatic cancer CSCs, positioning lncRNA FOXD1-AS1 as a promising therapeutic target for PC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cancer stem cell | |
| 650 | 4 | |a N6-methyladenosine, 5-FU | |
| 650 | 4 | |a Pancreatic cancer | |
| 650 | 4 | |a lncRNA FOXD1-AS1 | |
| 700 | 1 | |a Sun, Min-Min |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ping-Sheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Yi-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xin-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Wan-Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Zhen-Shun |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Kai |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Li-Xue |e verfasserin |4 aut | |
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