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肿瘤引流肺静脉中细胞外囊泡长链非编码RNA-p21的表达决定非小细胞肺癌的预后并调节内皮细胞行为。

Extracellular Vesicle lincRNA-p21 Expression in Tumor-Draining Pulmonary Vein Defines Prognosis in NSCLC and Modulates Endothelial Cell Behavior.

作者信息

Castellano Joan J, Marrades Ramon M, Molins Laureano, Viñolas Nuria, Moises Jorge, Canals Jordi, Han Bing, Li Yan, Martinez Daniel, Monzó Mariano, Navarro Alfons

机构信息

Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, School of Medicine, University of Barcelona, IDIBAPS, 08036 Barcelona, Spain.

Thoracic Oncology Unit, Hospital Clinic, 08036 Barcelona, Spain.

出版信息

Cancers (Basel). 2020 Mar 20;12(3):734. doi: 10.3390/cancers12030734.

DOI:10.3390/cancers12030734
PMID:32244977
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7140053/
Abstract

Hypoxia-induced upregulation of lincRNA-p21 in tumor tissue was previously shown by our group to be related to poor prognosis in resected non-small cell lung cancer (NSCLC) patients. In the present study, we have evaluated the presence of lincRNA-p21 in extracellular vesicles (EVs) from NSCLC patients and assessed its potential as a prognostic biomarker. High EV lincRNA-p21 levels in blood from the tumor-draining vein were associated with shorter time to relapse and shorter overall survival. Moreover, the multivariate analysis identified high lincRNA-p21 levels as an independent prognostic marker. In addition, lincRNA-p21 was overexpressed in H23 and HCC44 NSCLC cell lines and their derived EVs under hypoxic conditions. Functional assays using human umbilical vein endothelial cells (HUVECs) showed that tumor-derived EVs enriched in lincRNA-p21 affected endothelial cells by promoting tube formation and enhancing tumor cell adhesion to endothelial cells. Additionally, the analysis of selected EV microRNAs related to angiogenesis and metastasis showed that the microRNAs correlated with EV lincRNA-p21 levels in both patients and cell lines. Finally, EV co-culture with HUVEC cells increased the expression of microRNAs and genes related to endothelial cell activation. In conclusion, EV lincRNA-p21 acts as a novel prognosis marker in resected NSCLC patients, promoting angiogenesis and metastasis.

摘要

我们小组之前的研究表明，肿瘤组织中缺氧诱导的lincRNA-p21上调与接受手术切除的非小细胞肺癌（NSCLC）患者的不良预后相关。在本研究中，我们评估了NSCLC患者细胞外囊泡（EVs）中lincRNA-p21的存在情况，并评估了其作为预后生物标志物的潜力。肿瘤引流静脉血中EV lincRNA-p21水平较高与较短的复发时间和较短的总生存期相关。此外，多变量分析确定高lincRNA-p21水平是一个独立的预后标志物。此外，在缺氧条件下，lincRNA-p21在H23和HCC44 NSCLC细胞系及其衍生的EVs中过表达。使用人脐静脉内皮细胞（HUVECs）进行的功能分析表明，富含lincRNA-p21的肿瘤来源EVs通过促进管腔形成和增强肿瘤细胞与内皮细胞的粘附来影响内皮细胞。此外，对与血管生成和转移相关的选定EV微小RNA的分析表明，这些微小RNA在患者和细胞系中均与EV lincRNA-p21水平相关。最后，EV与HUVEC细胞共培养增加了与内皮细胞激活相关的微小RNA和基因的表达。总之，EV lincRNA-p21在接受手术切除的NSCLC患者中作为一种新的预后标志物，促进血管生成和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/d52e4bd3b737/cancers-12-00734-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/897dcad7de5e/cancers-12-00734-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/5e1545a3f488/cancers-12-00734-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/dc46f329a808/cancers-12-00734-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/d52e4bd3b737/cancers-12-00734-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/897dcad7de5e/cancers-12-00734-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/5e1545a3f488/cancers-12-00734-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/dc46f329a808/cancers-12-00734-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6de6/7140053/d52e4bd3b737/cancers-12-00734-g004.jpg

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