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Full Length Article | Open Access

JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1

Junping Liu1, Yutong Shi1, Minmin Wu1, Fengmei Zhang1, Mengqi Xu, Zhiqiang He, Min Tang( )
Key Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400016, China

1 These authors contributed equally to this work.

Peer review under responsibility of Chongqing Medical University.

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Abstract

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.

Keywords

AngiogenesisTriple-negative breast cancerExosomeJAG1lncRNAMALAT1

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Genes & Diseases
Volume 10 Issue 5,
September 2023
Pages 2167-2178
DOI: 10.1016/j.gendis.2022.07.006
Cite this article:
Liu J, Shi Y, Wu M, et al. JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1. Genes & Diseases, 2023, 10(5): 2167-2178. https://doi.org/10.1016/j.gendis.2022.07.006

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Received: 10 March 2022
Revised: 22 June 2022
Accepted: 16 July 2022
Published: 05 August 2022
© 2022 The Authors.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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