Rs41291957 polymorphism in the promoter region of microRNA-143 serves as a prognostic biomarker for patients with intracranial hemorrhage

The present study aimed to investigate the function of the single nucleotide polymorphism (SNP) rs41291957 in the prognosis of intracerebral hemorrhage (ICH). In addition, the molecular mechanisms underlying the role of microRNA (miR)-143, Toll-like receptor 2 (TLR2) and interleukin-16 (IL-16) were studied in patients with ICH that carried different alleles in the locus of the rs41291957 SNP. Kaplan-Meier survival curves were calculated for 182 patients with ICH, genotyped as CC, presenting a cytosine in both chromosome, CT, presenting both variants, and TT, presents a thymine in both chromosomes. In addition, the possible regulatory relationships between miR-143 and TLR2/IL-16 were studied using computational analysis, luciferase assays and western blot assay. In addition, the inflammatory profiles of cerebrospinal fluid (CSF) and serum samples collected from the subjects were compared. The patients genotyped as TT presented the lowest survival rate, while patients genotyped as CC presented the highest survival rate. TLR2 mRNA was identified as a potential target of miR-143, while IL-16 showed no direct interaction with miR-143. The above regulatory relationships were further investigated using cells transfected with miR-143 precursor or TLR2 small interfering RNA. In addition, the expression levels of inflammatory factors, such as tumor necrosis factor α, interferon, IL-6, IL-10 and NF-L-6, were highest in the CSF/serum samples collected from patients genotyped as TT and lowest in patients genotyped as CC. By contrast, the expression levels of miR-143 showed an opposite trend in the expression of the above inflammatory factors. The rs41291957 SNP, located in the promoter region of miR-143, reduced the expression of miR-143 and upregulated the expression of the pro-inflammatory factor TLR2, eventually leading to a poorer prognosis in patients with ICH.