Dataset Information

The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.

ABSTRACT: Homeobox transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA (lncRNA), has been considered to play critical roles in the biological properties of various tumors. The purposes of this study were to investigate the role and possible molecular mechanisms of HOTAIR in regulating the permeability of blood tumor barrier (BTB) in vitro. Our present study elucidated that the expressions of HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b-3p was down-regulated in glioma microvascular endothelial cells (GECs). Knockdown of HOTAIR could increase the permeability of BTB as well as down-regulated the expressions of tight junction related proteins ZO-1, occludin, claudin-5, but up-regulated miR-148b-3p expressions in GECs. Meanwhile, dual-luciferase reporter assays demonstrated that HOTAIR was a target RNA of miR-148b-3p. Furthermore, overexpression of miR-148b-3p increased the permeability of BTB by down-regulating the expressions of tight junction related proteins and USF1 in GECs, and vice versa. And further result revealed USF1 was a target of miR-148b-3p. Silence of USF1 increased the permeability of BTB duo to their interaction with the promoters of ZO-1, occludin, and claudin-5 in GECs. Taken together, our finding indicated that knockdown of HOTAIR increased BTB permeability via binding to miR-148b-3p, which further reducing tight junction related proteins in GECs by targeting USF1. Thus, HOTAIR will attract more attention since it can serve as a potential target of drug delivery across BTB and may provide novel strategies for glioma treatment.

SUBMITTER: Sa L

PROVIDER: S-EPMC5487514 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.

Sa Libo L Li Yan Y Zhao Lini L Liu Yunhui Y Wang Ping P Liu Libo L Li Zhen Z Ma Jun J Cai Heng H Xue Yixue Y

Frontiers in molecular neuroscience 20170628

Homeobox transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA (lncRNA), has been considered to play critical roles in the biological properties of various tumors. The purposes of this study were to investigate the role and possible molecular mechanisms of HOTAIR in regulating the permeability of blood tumor barrier (BTB) <i>in vitro</i>. Our present study elucidated that the expressions of HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b-3p was dow ...[more]

PMID: 28701916

Similar Datasets

Project description:BACKGROUND:Gain-of-function mutations and overexpression of KIT are characteristic features of gastrointestinal stromal tumor (GIST). Dysregulation in miRNA expression may lead to KIT overexpression and tumorigenesis. METHODS:miRNA microarray analysis and real-time PCR were used to determine the miRNA expression profiles in a cohort of 69 clinical samples including 50 CD117IHC+/KITmutation GISTs and 19 CD117IHC-/wild-type GISTs. GO enrichment and KEGG pathway analyses were performed to reveal the predicted targets of the dysregulated miRNAs. Of the dysregulated miRNAs whose expression was inversely correlated with that of KIT miRNAs were predicted by bioinformatics analysis and confirmed by luciferase reporter assay. Cell counting kit-8 (CCK-8) and flow cytometry were used to measure the cell proliferation, cycle arrest and apoptosis. Wound healing and transwell assays were used to evaluate migration and invasion. A xenograft BALB/c nude mouse model was applied to investigate the tumorigenesis in vivo. Western blot and qRT-PCR were used to investigate the protein and mRNA levels of KIT and its downstream effectors including ERK, AKT and STAT3. RESULTS:Of the six miRNAs whose expression was inversely correlated with that of KIT, we found that miR-148b-3p was significantly downregulated in the CD117IHC+/KITmutation GIST cohort. This miRNA was subsequently found to inhibit proliferation, migration and invasion of GIST882 cells. Mechanistically, miR-148b-3p was shown to regulate KIT expression through directly binding to the 3'-UTR of the KIT mRNA. Restoration of miR-148b-3p expression in GIST882 cells led to reduced expression of KIT and the downstream effectors proteins ERK, AKT and STAT3. However, overexpression of KIT reversed the inhibitory effect of miR-148b-3p on cell proliferation, migration and invasion. Furthermore, we found that reduced miR-148b-3p expression correlated with poor overall survival (OS) and disease-free survival (DFS) in GIST patients. CONCLUSION:miR-148b-3p functions as an important regulator of KIT expression and a potential prognostic biomarker for GISTs.

Dataset Information

The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.

Publications

The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets