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.
Highlights
Malignant glioma has been overwhelmingly considered as the most common primary tumor in the brain (Li et al, 2014)
There was no significant difference between control and miR-148b-3p (+) negative control (NC) + upstream stimulatory factor 1 (USF1) (+) NC group (P > 0.05)
Homeobox transcript antisense intergenic RNA (HOTAIR) was highly expressed in malignant gliomas tissues or U87 and U251 cells, and silence of HOTAIR decreased the abilities of proliferation, migration, and invasion as well as promoted cell apoptosis in glioma cells, and these influences on the biological behavior of glioma cells were achieved through the competitive inhibition of HOTAIR on miR-326-mediated targeting combination with FGF1 (Ke et al, 2015)
Summary
Malignant glioma has been overwhelmingly considered as the most common primary tumor in the brain (Li et al, 2014). HOTAIR is highly expressed in breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, gastric cancer, brain glioma and related to metastasis and poor prognosis of tumor, which strongly indicating HOTAIR plays carcinogenic role in the above mentioned cancer tissues (Gupta et al, 2010; Geng et al, 2011; Hajjari et al, 2013; Kim et al, 2013; Zhang et al, 2013; Zhuang et al, 2013). HOTAIR inhibited the regulatory role of miR331-3p in HER2 expression of gastric cancer tissue (Liu et al, 2014). All the above studies inferred that HOTAIR might inhibit the expressions of miRNAs and result in the changes of downstream related molecules to further regulate the biological function of cancer cells
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