Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway
Abstract 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 confi...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12943-024-01979-z |
| _version_ | 1797233776759144448 |
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| author | Zhiqiang He Yuhan Zhong Parbatraj Regmi Tianrun Lv Wenjie Ma Junke Wang Fei Liu Siqi Yang Yanjie Zhong Rongxing Zhou Yanwen Jin Nansheng Cheng Yujun Shi Haijie Hu Fuyu Li |
| author_facet | Zhiqiang He Yuhan Zhong Parbatraj Regmi Tianrun Lv Wenjie Ma Junke Wang Fei Liu Siqi Yang Yanjie Zhong Rongxing Zhou Yanwen Jin Nansheng Cheng Yujun Shi Haijie Hu Fuyu Li |
| author_sort | Zhiqiang He |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T16:21:33Z |
| format | Article |
| id | doaj.art-ad15313190b34b628f50edf34fb3e5e0 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-04-24T16:21:33Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-ad15313190b34b628f50edf34fb3e5e02024-03-31T11:12:10ZengBMCMolecular Cancer1476-45982024-03-0123112610.1186/s12943-024-01979-zExosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathwayZhiqiang He0Yuhan Zhong1Parbatraj Regmi2Tianrun Lv3Wenjie Ma4Junke Wang5Fei Liu6Siqi Yang7Yanjie Zhong8Rongxing Zhou9Yanwen Jin10Nansheng Cheng11Yujun Shi12Haijie Hu13Fuyu Li14Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityKey Laboratory of Transplant Engineering and Immunology, NHFPC, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityDivision of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan UniversityAbstract 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.https://doi.org/10.1186/s12943-024-01979-zTRPM2-ASGallbladder cancerAngiogenesisPABPC1NOTCH1IGF2BP2 |
| spellingShingle | Zhiqiang He Yuhan Zhong Parbatraj Regmi Tianrun Lv Wenjie Ma Junke Wang Fei Liu Siqi Yang Yanjie Zhong Rongxing Zhou Yanwen Jin Nansheng Cheng Yujun Shi Haijie Hu Fuyu Li Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway Molecular Cancer TRPM2-AS Gallbladder cancer Angiogenesis PABPC1 NOTCH1 IGF2BP2 |
| title | Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway |
| title_full | Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway |
| title_fullStr | Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway |
| title_full_unstemmed | Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway |
| title_short | Exosomal long non-coding RNA TRPM2-AS promotes angiogenesis in gallbladder cancer through interacting with PABPC1 to activate NOTCH1 signaling pathway |
| title_sort | exosomal long non coding rna trpm2 as promotes angiogenesis in gallbladder cancer through interacting with pabpc1 to activate notch1 signaling pathway |
| topic | TRPM2-AS Gallbladder cancer Angiogenesis PABPC1 NOTCH1 IGF2BP2 |
| url | https://doi.org/10.1186/s12943-024-01979-z |
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