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

作     者：Junping Liu Yutong Shi Minmin Wu Fengmei Zhang Mengqi Xu Zhiqiang He Min Tang Junping Liu;Yutong Shi;Minmin Wu;Fengmei Zhang;Mengqi Xu;Zhiqiiang He;Min Tang

作者机构：Key Laboratory of Laboratory Medical Diagnostics Designated by the Chinese Ministry of EducationChongqing Medical UniversityChongqing 400016China 

出 版 物：《Genes & Diseases》 (基因与疾病（英文）)

年 卷 期：2023年第10卷第5期

页      面：2167-2178页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Chongqing Medical University  CQMU 

主　　题：Angiogenesis Exosome JAG1 lncRNAMALAT1 Triple-negative breast cancer 

摘      要：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.