LncRNA DANCR attenuates brain microvascular endothelial cell damage induced by oxygen-glucose deprivation through regulating of miR-33a-5p/XBP1s

Mengqi Zhang,Zhuohui Chen,Zhuolu Wang,Jingyan Sun,Songfeng Zhao,Hui Ding,Xinhang Hu,Mimi Tang,Xinyi Lv,Bo Xiao,Shuntong Kang,Tong Wu,Qian Wu

doi:10.18632/aging.102712

Abstract

Brain microvascular endothelial cell (BMEC) survival and angiogenesis after ischemic stroke has great significance for improving the prognosis of stroke. Abnormal variants of lncRNAs are closely associated with stroke. In this study, we examined the effects and molecular mechanisms of differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis, migration, and angiogenesis of oxygen-glucose deprivation (OGD)-treated BMECs. We found that DANCR expression significantly increased at 2, 4, 6, 8, and 10 h after OGD. DANCR overexpression promoted cell viability, migration, and angiogenesis in OGD-treated BMECs. Additionally, we found that X-box binding protein l splicing (XBP1s) expression was positively correlated with DANCR expression. DANCR overexpression promoted XBP1s expression in OGD-treated BMECs. Silenced XBP1s reversed the effect of DANCR in OGD-treated BMECs. Furthermore, we found that microRNA (miR)-33a-5p bound to DANCR and the 3'-UTR of XBP1. miR-33a-5p overexpression inhibited proliferation, migration, angiogenesis, and XBP1s expression in OGD-treated DANCR-overexpressing BMECs, reversing the protective effect of DANCR. Finally, we found that XBP1s expression promoted proliferation, migration, and angiogenesis, reversing the damaging effect of miR-33a-5p. In conclusion, DANCR enhanced survival and angiogenesis in OGD-treated BMECs through the miR-33a-5p/XBP1s axis.

Highlights

Stroke causes neurological dysfunction and long-term disability, has a high incidence, and imposes an extremely heavy burden worldwide including in China [1, 2]
We found that Differentiation antagonizing non-protein coding RNA (DANCR) expression was upregulated in oxygen-glucose deprivation (OGD)-induced Brain microvascular endothelial cell (BMEC)
We found that DANCR promoted cell viability, cell migration, and angiogenesis, whereas silenced DANCR expression further inhibited cell viability, cell migration, and angiogenesis in OGD-treated BMECs

Summary

Introduction

Stroke causes neurological dysfunction and long-term disability, has a high incidence, and imposes an extremely heavy burden worldwide including in China [1, 2]. Much effort is being put into the development of new treatment strategies for ischemic stroke, thrombolytic therapy is currently the only effective treatment [4]. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long ncRNAs (lncRNAs), modulate gene expression and function through different mechanisms [5, 6]. LncRNAs may act as competing endogenous RNAs (ceRNAs) by interacting with miRNAs and regulating the expression of the miRNA www.aging-us.com target protein. In cerebral ischemic stroke, KCNQ1OT1 knockdown significantly decreases the infarct volume and improves neurological function by regulating miR-200a/FOXO3 and promoting autophagy [10]. Differentiation antagonizing non-protein coding RNA (DANCR) is an lncRNA located on chromosome 4q12 that maintains stemness and suppresses progenitor differentiation [11]. The role played by DANCR in ischemic stroke remains unclear

Methods

Results

Conclusion