Abstract
Ischemic stroke (IS) is a disease that is characterized by high mortality and disability. Recent studies have shown that LncRNA-mediated competing endogenous RNA (ceRNA) networks play roles in the occurrence and development of cerebral I/R injury by regulating different signaling pathways. However, no systematic analysis of ceRNA mechanisms in IS has been reported. In this review, we discuss molecular mechanisms of LncRNA-mediated ceRNA networks under I/R injury. The expression levels of LncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) and their effects in four major cell types of the neurovascular unit (NVU) are also involved. We further summarize studies of LncRNAs as biomarkers and therapeutic targets. Finally, we analyze the advantages and limitations of using LncRNAs as therapeutics for IS.
Highlights
Ischemic stroke (IS) is a neurological disorder that is characterized by blockage of blood vessels and accounts for approximately 87% of strokes (Fann et al, 2013; Lin et al, 2016; Kuriakose and Xiao 2020)
I/R injury leads to autophagy and apoptosis of BMECs, which accounts for bloodbrain barrier (BBB) disruption and enhances vascular permeability, resulting in an unfavorable prognosis among patients suffering from IS (Li et al, 2014)
The lack of oxygen and energy causes ion pump failure, apoptosis, inflammation, glutamate excitatory toxicity, and oxidative stress, which are harmful to the cell components of neurovascular unit (NVU), such as neurons, glial cells, BMECs, and astrocytes
Summary
Ischemic stroke (IS) is a neurological disorder that is characterized by blockage of blood vessels and accounts for approximately 87% of strokes (Fann et al, 2013; Lin et al, 2016; Kuriakose and Xiao 2020). LncRNAs can compete with an mRNA, bind to the same miRNA, and regulate the expression of the mRNA if they have the same MRE (Figure 1). We focus on LncRNAs that mediate ceRNA networks and regulate key processes involved in I/R injury to explore the potential roles of LncRNAs in regulating IS. Recent studies have shown that LncRNAs, such as lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), play important roles in IS (Zhang et al, 2017a). Another class of non-coding RNAs is microRNAs (miRNAs), which are single-stranded endogenous RNAs with a length of 19–25 nt (Lu and Rothenberg 2018). CeRNAs can competitively bind to the same miRNA by interacting with miRNA response elements (MREs) to build communication networks between messenger RNAs and non-coding RNAs
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