LncRNAs Stand as Potent Biomarkers and Therapeutic Targets for Stroke

Abstract

Stroke is a major public health problem worldwide with a high burden of neurological disability and mortality. Long noncoding RNAs (lncRNAs) have attracted much attention in the past decades because of their newly discovered roles in pathophysiological processes in many diseases. The abundance of lncRNAs in the nervous system indicates that they may be part of a complex regulatory network governing physiology and pathology of the brain. In particular, lncRNAs have been shown to play pivotal roles in the pathogenesis of stroke. In this article, we provide a review of the multifaceted functions of lncRNAs in the pathogenesis of ischemic stroke and intracerebral hemorrhage, highlighting their promising use as stroke diagnostic biomarkers and therapeutics. To this end, we discuss the potential of stem cells in aiding lncRNA applications in stroke.

Saposhnikoviae Radix Enhanced the Angiogenic and Anti-Inflammatory Effects of Huangqi Chifeng Tang in a Rat Model of Cerebral Infarction

“…CI is a local ischemic condition characterized by decreased cerebral blood flow and vascular embolism [ 17 ]. In the ischemic state, brain tissue is insufficiently supplied with oxygen and nutrients due to restrained and reduced blood flow, which results in a series of inflammatory responses, severe oxidative stress, neuronal damage, and apoptosis [ 18 , 19 ].…”

Emerging Role of LncRNAs in Ischemic Stroke—Novel Insights into the Regulation of Inflammation

“…Among the various programmed cell death pathways, 64 apoptosis accounts for a large proportion of neuronal death through brain ischemia, 65 which efficiently removes damaged cells from DNA damage or during development. 66 Apoptosis plays a pivotal role in the homeostasis of normal tissues, and researchers have recently found that lncRNAs have essential effects on regulating cell apoptosis following stroke. 67 LncRNA growth arrest-specific 5 (GAS5), a ceRNA for miR137, was upregulated and negatively correlated with miR137 expression in stroke mice and OGD/R-treated primary neurons.…”

“… 67 It is widely accepted that various lncRNAs affect cell survival in stroke by regulating autophagy. 66 MALAT1 is one of the most significantly upregulated lncRNAs in both in vivo and in vitro models of stroke and serves as a competing endogenous RNA by sponging miR-126 to upregulate its target ULK2 under hypoxic injury based on the protective effect of autophagy. 47 Similarly, lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) and lncRNA FosDT were all elevated by negatively regulating miR-127 expression 80 and interacting with REST-associated chromatin-modifying proteins separately to protect against ischemic stroke.…”

“…A large number of studies have illustrated that various lncRNAs are closely associated with the regulation of inflammation and microglial activation in ischemia. 66 Several studies have revealed that knocking down lncRNA MALAT1 reduces inflammatory damage after ischemia by Myd88 signaling while overexpressing lncRNA MALAT1 is positively associated with higher levels of interleukin (IL-1β), tumor necrosis factor α (TNF-α) and IL-6. 122 H19 is one of the most representative lncRNA genes that can be activated after hypoxia, and it can potentially increase inflammation.…”

Development and Validation of a LASSO Prediction Model for Better Identification of Ischemic Stroke: A Case-Control Study in China

“…As a result, more attention has been paid to blood biomarkers that can be objectively measured in the laboratory at hyperacute phase, hoping to assist in the accurate identification of ISs. The application of fast, reliable, and inexpensive blood biomarkers as an auxiliary tool, along with CT characteristics, would provide more diagnostic information that may improve stroke identification and management, especially in atypical or hyperacute IS ( Wu et al, 2019 ; Fan et al, 2020 ; Baez et al, 2021 ).…”