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

作者全名："Liu, Junping; Shi, Yutong; Wu, Minmin; Zhang, Fengmei; Xu, Mengqi; He, Zhiqiang; Tang, Min"

作者地址："[Liu, Junping; Shi, Yutong; Wu, Minmin; Zhang, Fengmei; Xu, Mengqi; He, Zhiqiang; Tang, Min] Chongqing Med Univ, Chinese Minist Educ, Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China"

通信作者："Tang, M (通讯作者)，Chongqing Med Univ, Chinese Minist Educ, Key Lab Lab Med Diagnost, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001037513000001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：10

期号：5

开始页：2167

结束页：2178

文献类型：Article

关键词：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-1405p-JAG1/VEGFA pathway."

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