Junping Liu, Yutong Shi, Minmin Wu, et al. JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1. [J]. Genes & Diseases 10(5).(2023)
DOI:
Junping Liu, Yutong Shi, Minmin Wu, et al. JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1. [J]. Genes & Diseases 10(5).(2023) DOI: 10.1016/j.gendis.2022.07.006.
JAG1 enhances angiogenesis in triple-negative breast cancer through promoting the secretion of exosomal lncRNA MALAT1
摘要
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.
关键词
Keywords
AngiogenesisExosomeJAG1lncRNAMALAT1Triple-negative breast cancer
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