机构：[1]Department of neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[2]Department of neurosurgery, Fuxing Hospital, Capital Medical University, Beijing 100050, P.R. China[3]Core Laboratory for Clinical Medical Research, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China首都医科大学附属天坛医院[4]Metastasis and Angiogenesis Research Group, University Department of Surgery, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK
The blood-brain barrier (BBB) constitutes an efficient organization of tight junctions that limits the delivery of tumor to the brain. The principal tight junction protein in BBB is claudin-5 (CLDN5), but its mechanism of action remains largely unknown. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers, some lncRNAs play key roles in regulating BBB permeability and are involved in tumor brain metastasis. In particular, lncRNAs can function as competing endogenous RNAs (ceRNAs). Herein, we investigated whether ceRNA dysregulation is associated with alterations of the level of CLDN5 in human brain vascular endothelial hCMEC/D3 cells. The Affymetrix Human Transcriptome Array 2.0 and Affymetrix GeneChip miRNA 4.0 Array were used to detect the expression levels of 2,578 miRNAs, 22,829 lncRNAs, and 44,699 mRNAs in pLL3.7-CLDN5-transfected and pLL3.7 control hCMEC/D3 cells. The distinctly expressed miRNAs, lncRNAs, and mRNAs were subjected to construction of miRNA-lncRNA-mRNA interaction network. A total of 41 miRNAs, 954 lncRNAs, and 222 mRNAs were found to be differentially expressed between the CLDN5-overexpressing and control group. 148 lncRNA acting as ceRNAs were identified based on the miRNA-lncRNA-mRNA interaction network. The function of differential mRNA in the network was determined by GO and pathway analysis. The potential roles of the 27 ceRNAs were revealed, the possible biology functions of these regulatory ceRNAs mainly included tight junction, focal adhesion, cell-cell adhesion, cell growth and apoptosis. The identified sets of miRNAs, lncRNAs and mRNAs specific to CLDN5-overexpressing hCMEC/D3 cells were verified by quantitative real-time RT-PCR experiment. Our study predicts the biological functions of a multitude of ceRNAs associated with the alteration of CLDN5 in brain vascular endothelial cells. Our data suggest that these dysregulated ceRNAs, in conjunction with the high CLDN5 levels, could serve as useful targets of prevention of brain metastasis formation. Further studies are warranted to determine the role of these ceRNAs in facilitating the function of CLDN5 in brain-tumor barrier.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81471229]; Natural Science Foundation of Beijing CityBeijing Natural Science Foundation [7152098, 7142054]
第一作者机构：[1]Department of neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China[2]Department of neurosurgery, Fuxing Hospital, Capital Medical University, Beijing 100050, P.R. China
共同第一作者：
通讯作者：
通讯机构：[1]Department of neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China[*1]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Beijing 100050, P.R. China
推荐引用方式(GB/T 7714)：
Shun-chang Ma,Qi Li,Jia-yi Peng,et al.CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood-brain barrier permeability in tumor brain metastasis[J].ONCOLOGY REPORTS.2018,39(3):1441-1453.doi:10.3892/or.2018.6208.
APA：
Shun-chang Ma,Qi Li,Jia-yi Peng,Jian-long Zhouwen,Dai-nan Zhang...&Wang Jia.(2018).CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood-brain barrier permeability in tumor brain metastasis.ONCOLOGY REPORTS,39,(3)
MLA：
Shun-chang Ma,et al."CLDN5 affects lncRNAs acting as ceRNA dynamics contributing to regulating blood-brain barrier permeability in tumor brain metastasis".ONCOLOGY REPORTS 39..3(2018):1441-1453
