Pumilio RNA-Binding Family Member 1 Plays a Promoting Role on Pancreatic Cancer Angiogenesis

Pumilio RNA-Binding Family Member 1 Plays a Promoting Role on Pancreatic Cancer Angiogenesis
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Pumilio RNA 结合家族成员 1 在胰腺癌血管生成中发挥促进作用

DOI:
10.1155/2022/9202531
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发表时间:
2022-12-14
影响因子:
2.7
通讯作者:
Chen,Zhiyu
Chen,Zhiyu
中科院分区:
医学4区
文献类型:
--
作者:
Dai,Haisu;Jiang,Yan;Chen,Zhiyu

文献摘要

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我们先前的研究表明,Pumilio RNA结合家族成员1(Pumilio RNA结合家族成员1,Pumilio RNA结合家族成员1)基因在胰腺癌(PC)组织中异常表达,其敲低抑制PC细胞的生长和转移。在这里,我们旨在进一步研究其在血管生成中的作用。进行免疫组织化学测定以分析PC组织和皮下异种移植肿瘤中CD 31和PUM 1的表达水平。PC组织中的CD 31水平表示为微血管密度(MVD)。MVD值与MVD 1蛋白表达呈正相关。在PC细胞系中成功地过表达或沉默了p53 1。与PC细胞共培养时,HUVECs的增殖、迁移、侵袭和管形成能力增强。在PC细胞中,VEGFA 1过表达增加细胞外和细胞内VEGFA蛋白水平。此外,当HUVECs与过表达PDE1的PC细胞共培养时,HUVECs中的血管生成相关信号被激活。然而,PC细胞沉默与EST1有相反的效果。此外,过表达CD31的皮下异种移植肿瘤具有较高的CD31表达水平,而沉默CD31的皮下异种移植肿瘤具有较低的CD31表达水平。结论:PC细胞中的BMP1可能在PC血管生成中起促进作用。BMP1可能是PC细胞中一种新的血管生成调节因子。
Our previous studies showed that Pumilio RNA‐binding family member 1 (PUM1) gene is abnormally expressed in pancreatic cancer (PC) tissues, and its knockdown suppresses the growth and metastasis of PC cells. Here, we aimed to further investigate its role in angiogenesis. Immunohistochemical assays were carried out to analyze CD31 and PUM1 expression levels in PC tissues and in subcutaneous xenograft tumors. CD31 levels in PC tissues are expressed as microvessel density (MVD). MVD value was positively correlated with PUM1 protein expression. PUM1 was successfully overexpressed or silenced in the PC cell lines. The proliferation, migration, invasion, and tube formation ability of HUVECs were enhanced when cocultured with PC cells overexpressing PUM1. PUM1 overexpression increased extracellular and intracellular VEGFA protein levels in PC cells. Moreover, angiogenesis‐related signaling in HUVECs was activated when HUVECs were cocultured with PC cells overexpressing PUM1. Nevertheless, PC cells silenced with PUM1 had the opposite effect. Moreover, subcutaneous xenograft tumors overexpressing PUM1 have the higher expression level of CD31, while subcutaneous xenograft tumors silencing PUM1 have the lower expression level of CD31. In conclusion, PUM1 in PC cells may play a promoting role in PC angiogenesis. PUM1 may be a new regulator of angiogenesis in PC cells.