CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation
Abstract Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor prognosis. LncRNA MAPKAPK5-AS1 is a potential oncogene and contributes to HCC cell malignant proliferation. This study explores the role of MAPKAPK5-AS1 carried by carcinoma-associated fibroblasts-derived extracellular ves...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07428-3 |
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| author | Lin Sheng Junmei Lin Yili Zhang Yanping Chen Xuxing Ye Xiaobo Wang |
| author_facet | Lin Sheng Junmei Lin Yili Zhang Yanping Chen Xuxing Ye Xiaobo Wang |
| author_sort | Lin Sheng |
| collection | DOAJ |
| description | Abstract Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor prognosis. LncRNA MAPKAPK5-AS1 is a potential oncogene and contributes to HCC cell malignant proliferation. This study explores the role of MAPKAPK5-AS1 carried by carcinoma-associated fibroblasts-derived extracellular vesicles (CAF-EVs) in HCC cell proliferation. Our findings reveal that CAF-EVs promotes HCC cell proliferation by delivering MAPKAPK5-AS1, which binds to and inhibits SMURF2 and stabilizes TCF12. SMURF2 leads to TCF12 ubiquitination and degradation. TCF12 upregulates FOXH1 expression. In animal model, CAF-EVs enhances tumor growth by stabilizing TCF12 via MAPKAPK5-AS1 and activating FOXH1 transcription. In conclusion, CAF-EVs carrying MAPKAPK5-AS1 stabilizes TCF12 expression by competitively inhibiting SMURF2, thus promoting TCF12-mediated FOXH1 transcription and driving HCC cell proliferation. Our findings may offer insights for HCC treatment and suggest potential targets for future treatments, opening avenues for HCC therapies. |
| format | Article |
| id | doaj-art-ae5835c022ae4567b0b13127261e2eba |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-ae5835c022ae4567b0b13127261e2eba2025-01-05T12:43:17ZengNature PortfolioCommunications Biology2399-36422024-12-017111510.1038/s42003-024-07428-3CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferationLin Sheng0Junmei Lin1Yili Zhang2Yanping Chen3Xuxing Ye4Xiaobo Wang5The department of internal medicine, Jinhua Municipal Central HospitalDepartment of Traditional Chinese Medicine, Jinhua Municipal Central HospitalDepartment of Health Management Center, Affiliated Jinhua Hospital, Zhejiang University School of MedicineDepartment of Gastroenterology, Jinhua Municipal Central HospitalDepartment of Traditional Chinese Medicine, Jinhua Municipal Central HospitalThe Fourth School of Clinical Medicine, Zhejiang Chinese Medical UniversityAbstract Hepatocellular carcinoma (HCC) is an aggressive malignancy with poor prognosis. LncRNA MAPKAPK5-AS1 is a potential oncogene and contributes to HCC cell malignant proliferation. This study explores the role of MAPKAPK5-AS1 carried by carcinoma-associated fibroblasts-derived extracellular vesicles (CAF-EVs) in HCC cell proliferation. Our findings reveal that CAF-EVs promotes HCC cell proliferation by delivering MAPKAPK5-AS1, which binds to and inhibits SMURF2 and stabilizes TCF12. SMURF2 leads to TCF12 ubiquitination and degradation. TCF12 upregulates FOXH1 expression. In animal model, CAF-EVs enhances tumor growth by stabilizing TCF12 via MAPKAPK5-AS1 and activating FOXH1 transcription. In conclusion, CAF-EVs carrying MAPKAPK5-AS1 stabilizes TCF12 expression by competitively inhibiting SMURF2, thus promoting TCF12-mediated FOXH1 transcription and driving HCC cell proliferation. Our findings may offer insights for HCC treatment and suggest potential targets for future treatments, opening avenues for HCC therapies.https://doi.org/10.1038/s42003-024-07428-3 |
| spellingShingle | Lin Sheng Junmei Lin Yili Zhang Yanping Chen Xuxing Ye Xiaobo Wang CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation Communications Biology |
| title | CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation |
| title_full | CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation |
| title_fullStr | CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation |
| title_full_unstemmed | CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation |
| title_short | CAF-EVs carry lncRNA MAPKAPK5-AS1 into hepatocellular carcinoma cells and promote malignant cell proliferation |
| title_sort | caf evs carry lncrna mapkapk5 as1 into hepatocellular carcinoma cells and promote malignant cell proliferation |
| url | https://doi.org/10.1038/s42003-024-07428-3 |
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