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.

中文翻译：

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乳腺癌细胞中的Linc-OIP5通过YAP1 / Notch / NRP1信号通路在肿瘤微环境下调节人脐静脉内皮细胞的血管生成。

背景技术已经发现LincRNA与各种肿瘤发生和癌症发展密切相关，但是几乎没有研究特异性lincRNA在肿瘤相关血管生成中的作用。在这里，我们旨在调查乳腺癌细胞中的linc-OIP5是否影响HUVEC的血管生成，以及linc-OIP5法规是否参与了与血管生成相关的Notch和Hippo信号通路。方法采用trans-well系统共培养HUVECs与Lin-OIP5敲低乳腺癌细胞MDA-MB-231，研究HUVECs在乳腺癌细胞及其条件下的增殖，迁移和管形成能力以及相关信号指标的变化。培养基通过一系列细胞和分子实验。结果过表达的linc-OIP5，YAP1，在乳腺癌细胞MCF7和MDA-MB-231中发现了JAP1和JAG1，YAP1和JAG1的表达水平与乳腺癌组织的等级成正比。具有linc-OIP5敲低的MDA-MB-231细胞导致共培养的HUVEC的增殖，迁移和管形成能力减弱。此外，共培养的MDA-MB-231细胞中的linc-OIP5敲低显示YAP1和JAG1表达下调，同时在条件培养基中JAG1水平降低。此外，在这种条件下，还发现了共培养的HUVECs中破坏了DLL4 / Notch / NRP1的信号。结论因此，MDA-MB-231乳腺癌细胞中的linc-OIP5可能作用于YAP1 / Notch / NRP1信号回路的上游，从而以非细胞直接接触的方式影响共培养的HUVEC的增殖，迁移和管形成。在条件培养基中通过JAG1的方式。