Association Between Genetic Variants in the lncRNA–p53 Regulatory Network and Ischemic Stroke Prognosis

Abstract

Objective Recently, lncRNAs have been demonstrated to be associated with the p53 regulatory pathway,which serve as regulators or effectors. LncRNA-p53 regulatory network play important role in ischemia induced apoptosis and be importance for post-stroke recovery.Method Eight genetic variants in p53 related lncRNA were genotype in 940 patients to explore the association of SNPs in p53 regulatory pathway genes with ischemic stroke prognosis in a northern Chinese population. Long-term outcome and short-term outcome were respectively assessed by the stroke recurrence and modi ed Rankin Scale score at 3 months after stroke.Results We rst identi ed for that p53 rs1042522 and LINC-ROR rs2027701 may be associated with the risk of IS recurrence. In our further cumulative effect analysis, we found that these two polymorphisms may jointly be associated with IS recurrence. Patients carrying 2-4 risk alleles had signi cantly increased risk of IS recurrence compared with those carrying 0-1 risk alleles. In contrast to rs2027701 and rs1042522, other SNP was found to be not associated with IS recurrence. Subsequently, we also found that TUG1 rs2240183 CC genotype was associated with favorable outcome of ischemic stroke after adjusting confound factors. However, the other seven genetic variants in p53 related lncRNA were not associated with functional outcome after stroke.Conclusion P53 rs1042522 and LINC-ROR rs2027701 may have combined effects on IS recurrence and TUG1 rs2240183 may be new biomarker to predict the short-term outcome of ischemic stroke through modulating p53-mediated apoptosis.

Taurine-Upregulated Gene 1 Attenuates Cerebral Angiogenesis following Ischemic Stroke in Rats

“…They have also confirmed that the serum TUG1 level of diabetic patients with ischemic stroke is significantly higher than that of diabetic patients without ischemic stroke, and the serum TUG1 level is positively correlated with the NIHSS score of the patients [ 14 ]. TUG1 rs2240183 may be used as a new biomarker to predict the short-term prognosis of patients with ischemic stroke [ 28 ]. In acute ischemic stroke, lncRNA TUG1 can enhance neuronal damage mediated by ERK12 signal pathway [ 29 ].…”

Genetics of ischemic stroke functional outcome

“…One group showed that the C allele of rs2240183, a SNP in the TUG1 promoter region, led to increased TUG1 expression and IS risk which is in align with the aforementioned preclinical evidence [ 287 ]. However, Liu et al reported the CC genotype as protective with respect to 3-month mRS scores [ 179 ], thus further investigation is required to confirm the effects of rs2240183 on TUG1 activity and resultant changes in IS risk and outcome.…”

Functional Relevance of the Long Intergenic Non-Coding RNA Regulator of Reprogramming (Linc-ROR) in Cancer Proliferation, Metastasis, and Drug Resistance

“…Conversely, Hasemian et al [ 82 ] also quantified expression levels of lncRNAs in the peripheral blood of epileptic patients and found no significant difference in the expression of linc-ROR between patients and controls. In a different study, the p53 regulatory pathway was correlated with linc-ROR upregulation in ischemia-induced apoptosis, exerting a combined effect on ischemic stroke recurrence [ 83 ]. Similarly, expression of linc-ROR increased significantly in middle cerebral artery occlusion in mice and it also promoted ASK-1/STRAP/14-3-3 complex formation to inhibit the activation of TNF-α/ASK-1-mediated apoptosis of human brain microvascular endothelial cells, indicating a potential role in cerebral hypoxia-induced injury [ 84 ].…”