The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN
© 2024. The Author(s)..
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear.
METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1.
RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells.
CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Molecular cancer - 23(2024), 1 vom: 16. März, Seite 55 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jiang, Tao [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 03.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12943-024-01962-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369810287 |
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| 100 | 1 | |a Jiang, Tao |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The m6A modification mediated-lncRNA POU6F2-AS1 reprograms fatty acid metabolism and facilitates the growth of colorectal cancer via upregulation of FASN |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 18.03.2024 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear | ||
| 520 | |a METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1 | ||
| 520 | |a RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells | ||
| 520 | |a CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Fatty acid metabolism | |
| 650 | 4 | |a Growth | |
| 650 | 4 | |a POU6F2-AS1 | |
| 650 | 7 | |a RNA, Long Noncoding |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Fatty Acids |2 NLM | |
| 650 | 7 | |a POU6F2 protein, human |2 NLM | |
| 650 | 7 | |a POU Domain Factors |2 NLM | |
| 650 | 7 | |a METTL3 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.1.1.62 |2 NLM | |
| 650 | 7 | |a Methyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a FASN protein, human |2 NLM | |
| 650 | 7 | |a EC 2.3.1.85 |2 NLM | |
| 650 | 7 | |a Fatty Acid Synthase, Type I |2 NLM | |
| 650 | 7 | |a EC 2.3.1.85 |2 NLM | |
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| 700 | 1 | |a Xue, Zhenyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Bowen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jianquan |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Qihang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Hu |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Teng |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Ruizhi |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jun |e verfasserin |4 aut | |
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