JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1
Despite significant improvements in five-year survival rates due to early diagnosis and combination therapy, triple-negative breast cancer (TNBC) treatment remains a major challenge. Finding new and effective targets for diagnosis and drug therapy is urgent for TNBC patients. Jagged-1 (JAG1), one of...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2023-09-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304222002021 |
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| author | Junping Liu Yutong Shi Minmin Wu Fengmei Zhang Mengqi Xu Zhiqiang He Min Tang |
| author_facet | Junping Liu Yutong Shi Minmin Wu Fengmei Zhang Mengqi Xu Zhiqiang He Min Tang |
| author_sort | Junping Liu |
| collection | DOAJ |
| description | Despite significant improvements in five-year survival rates due to early diagnosis and combination therapy, triple-negative breast cancer (TNBC) treatment remains a major challenge. Finding new and effective targets for diagnosis and drug therapy is urgent for TNBC patients. Jagged-1 (JAG1), one of the canonical ligands of the Notch signaling pathway, is involved in vascular budding and is a poor prognostic factor of TNBC. In this study, combined with quantitative real-time PCR, database analysis, animal experiments, and other means, JAG1 was confirmed to be related to the poor prognosis of TNBC patients. JAG1 was highly expressed in MDA-MB-231 Bone (231B) cells, with stronger invasion and metastasis ability than MDA-MB-231 (231) cells. Treatment of human vascular endothelial cells (HUVEC) with TNBC conditioned medium showed that TNBC JAG1 promoted the angiogenesis of HUVEC. Next, we detected the exosomes extracted from TNBC conditioned medium and found that JAG1 promoted the exosome secretion from 231 cells via ALIX-RAB11A/RAB35. In addition, we also found that the exosomes from JAG1 overexpressed TNBC cells contained more long non-coding RNA (lncRNA) MALAT1, and MALAT1 promoted angiogenesis of HUVEC by targeting miR-140-5p. Finally, the angiogenesis-promoting effect of JAG1 in TNBC was further investigated by matrix gel assay. In conclusion, we reveal that JAG1 has a pro-invasion effect on TNBC and is involved in microenvironment angiogenesis by promoting exosome secretion and the MALAT1-miR-140-5p-JAG1/VEGFA pathway. |
| first_indexed | 2024-03-13T00:14:44Z |
| format | Article |
| id | doaj.art-abc393386b16458fab4962b2adc11028 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-13T00:14:44Z |
| publishDate | 2023-09-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-abc393386b16458fab4962b2adc110282023-07-12T04:19:36ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422023-09-0110521672178JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1Junping Liu0Yutong Shi1Minmin Wu2Fengmei Zhang3Mengqi Xu4Zhiqiang He5Min Tang6Key Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaKey Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaKey Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaKey Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaKey Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaKey Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaCorresponding author.; Key Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, ChinaDespite significant improvements in five-year survival rates due to early diagnosis and combination therapy, triple-negative breast cancer (TNBC) treatment remains a major challenge. Finding new and effective targets for diagnosis and drug therapy is urgent for TNBC patients. Jagged-1 (JAG1), one of the canonical ligands of the Notch signaling pathway, is involved in vascular budding and is a poor prognostic factor of TNBC. In this study, combined with quantitative real-time PCR, database analysis, animal experiments, and other means, JAG1 was confirmed to be related to the poor prognosis of TNBC patients. JAG1 was highly expressed in MDA-MB-231 Bone (231B) cells, with stronger invasion and metastasis ability than MDA-MB-231 (231) cells. Treatment of human vascular endothelial cells (HUVEC) with TNBC conditioned medium showed that TNBC JAG1 promoted the angiogenesis of HUVEC. Next, we detected the exosomes extracted from TNBC conditioned medium and found that JAG1 promoted the exosome secretion from 231 cells via ALIX-RAB11A/RAB35. In addition, we also found that the exosomes from JAG1 overexpressed TNBC cells contained more long non-coding RNA (lncRNA) MALAT1, and MALAT1 promoted angiogenesis of HUVEC by targeting miR-140-5p. Finally, the angiogenesis-promoting effect of JAG1 in TNBC was further investigated by matrix gel assay. In conclusion, we reveal that JAG1 has a pro-invasion effect on TNBC and is involved in microenvironment angiogenesis by promoting exosome secretion and the MALAT1-miR-140-5p-JAG1/VEGFA pathway.http://www.sciencedirect.com/science/article/pii/S2352304222002021AngiogenesisExosomeJAG1lncRNAMALAT1Triple-negative breast cancer |
| spellingShingle | Junping Liu Yutong Shi Minmin Wu Fengmei Zhang Mengqi Xu Zhiqiang He Min Tang JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1 Genes and Diseases Angiogenesis Exosome JAG1 lncRNAMALAT1 Triple-negative breast cancer |
| title | JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1 |
| title_full | JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1 |
| title_fullStr | JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1 |
| title_full_unstemmed | JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1 |
| title_short | JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1 |
| title_sort | jag1 enhances angiogenesis in triple negative breast cancer through promoting the secretion of exosomal lncrna malat1 |
| topic | Angiogenesis Exosome JAG1 lncRNAMALAT1 Triple-negative breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2352304222002021 |
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