Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway
© 2024. The Author(s)..
BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking.
METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1.
RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect.
CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.
| 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: 27. März, Seite 65 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Zhiqiang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 28.03.2024 Date Revised 03.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s12943-024-01979-z |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370219813 |
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| 024 | 7 | |a 10.1186/s12943-024-01979-z |2 doi | |
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| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a He, Zhiqiang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 28.03.2024 | ||
| 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: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking | ||
| 520 | |a METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1 | ||
| 520 | |a RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect | ||
| 520 | |a CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Angiogenesis | |
| 650 | 4 | |a Exosome | |
| 650 | 4 | |a Gallbladder cancer | |
| 650 | 4 | |a IGF2BP2 | |
| 650 | 4 | |a NOTCH1 | |
| 650 | 4 | |a PABPC1 | |
| 650 | 4 | |a TRPM2-AS | |
| 650 | 7 | |a RNA, Long Noncoding |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a TRPM Cation Channels |2 NLM | |
| 650 | 7 | |a RNA, Messenger |2 NLM | |
| 650 | 7 | |a NOTCH1 protein, human |2 NLM | |
| 650 | 7 | |a Receptor, Notch1 |2 NLM | |
| 650 | 7 | |a IGF2BP2 protein, human |2 NLM | |
| 650 | 7 | |a RNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a TRPM2 protein, human |2 NLM | |
| 650 | 7 | |a TRPM2 protein, mouse |2 NLM | |
| 700 | 1 | |a Zhong, Yuhan |e verfasserin |4 aut | |
| 700 | 1 | |a Regmi, Parbatraj |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Tianrun |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Wenjie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Junke |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Siqi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhong, Yanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Rongxing |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yanwen |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Nansheng |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yujun |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Haijie |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Fuyu |e verfasserin |4 aut | |
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