Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment

Abstract Background: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angioge...

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Autores principales: Zhu,Qing, Li,Jingchao, Wu,Qi, Cheng,Yongxia, Zheng,Huizhe, Zhan,Tao, Wang,Hongwei, Yang,Yue, Wang,Hongyan, Liu,Ye, Guo,Sufen
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2020
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100204
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spelling oai:scielo:S0716-976020200001002042020-06-25Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironmentZhu,QingLi,JingchaoWu,QiCheng,YongxiaZheng,HuizheZhan,TaoWang,HongweiYang,YueWang,HongyanLiu,YeGuo,Sufen Tumor microenvironment Angiogenesis Linc-OIP5 Signal transduction Breast cancer HUVECs Abstract Background: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. Methods: A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. Results: Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. Conclusion: Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.53 20202020-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100204en10.1186/s40659-020-0273-0
institution Scielo Chile
collection Scielo Chile
language English
topic Tumor microenvironment
Angiogenesis
Linc-OIP5
Signal transduction
Breast cancer
HUVECs
spellingShingle Tumor microenvironment
Angiogenesis
Linc-OIP5
Signal transduction
Breast cancer
HUVECs
Zhu,Qing
Li,Jingchao
Wu,Qi
Cheng,Yongxia
Zheng,Huizhe
Zhan,Tao
Wang,Hongwei
Yang,Yue
Wang,Hongyan
Liu,Ye
Guo,Sufen
Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment
description Abstract Background: LincRNAs have been revealed to be tightly associated with various tumorigeneses and cancer development, but the roles of specific lincRNA on tumor-related angiogenesis was hardly studied. Here, we aimed to investigate whether linc-OIP5 in breast cancer cells affects the angiogenesis of HUVECs and whether the linc-OIP5 regulations are involved in angiogenesis-related Notch and Hippo signaling pathways. Methods: A trans-well system co-cultured HUVECs with linc-OIP5 knockdown breast cancer cell MDA-MB-231 was utilized to study the proliferation, migration and tube formation abilities of HUVECs and alterations of related signaling indicators in breast cancer cells and their conditioned medium through a series of cell and molecular experiments. Results: Overexpressed linc-OIP5, YAP1, and JAG1 were found in breast cancer cell lines MCF7 and MDA-MB-231 and the expression levels of YAP1 and JAG1 were proportional to the breast cancer tissue grades. MDA-MB-231 cells with linc-OIP5 knockdown led to weakened proliferation, migration, and tube formation capacity of co-cultured HUVECs. Besides, linc-OIP5 knockdown in co-cultured MDA-MB-231 cells showed downregulated YAP1 and JAG1 expression, combined with a reduced JAG1 level in conditioned medium. Furthermore, a disrupted DLL4/Notch/NRP1 signaling in co-cultured HUVECs were also discovered under this condition. Conclusion: Hence, linc-OIP5 in MDA-MB-231 breast cancer cells may act on the upstream of the YAP1/Notch/NRP1 signaling circuit to affect proliferation, migration, and tube formation of co-cultured HUVECs in a non-cellular direct contact way through JAG1 in conditioned medium. These findings at least partially provide a new angiogenic signaling circuit in breast cancers and suggest linc-OIP5 could be considered as a therapeutic target in angiogenesis of breast cancers.
author Zhu,Qing
Li,Jingchao
Wu,Qi
Cheng,Yongxia
Zheng,Huizhe
Zhan,Tao
Wang,Hongwei
Yang,Yue
Wang,Hongyan
Liu,Ye
Guo,Sufen
author_facet Zhu,Qing
Li,Jingchao
Wu,Qi
Cheng,Yongxia
Zheng,Huizhe
Zhan,Tao
Wang,Hongwei
Yang,Yue
Wang,Hongyan
Liu,Ye
Guo,Sufen
author_sort Zhu,Qing
title Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment
title_short Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment
title_full Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment
title_fullStr Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment
title_full_unstemmed Linc-OIP5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through YAP1/Notch/NRP1 signaling circuit at a tumor microenvironment
title_sort linc-oip5 in the breast cancer cells regulates angiogenesis of human umbilical vein endothelial cells through yap1/notch/nrp1 signaling circuit at a tumor microenvironment
publisher Sociedad de Biología de Chile
publishDate 2020
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602020000100204
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