Yang Xiaobo, Guo Zongduo, Cao Fang, Teng Zhipeng, Huang Zhijian, Sun Xiaochuan
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.
Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 563000, P.R. China.
Mol Med Rep. 2021 Apr;23(4). doi: 10.3892/mmr.2021.11928. Epub 2021 Mar 2.
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.
本研究旨在探讨单核苷酸多态性(SNP)rs41291957在脑出血(ICH)预后中的作用。此外,还研究了在rs41291957 SNP位点携带不同等位基因的ICH患者中,微小RNA(miR)-143、Toll样受体2(TLR2)和白细胞介素-16(IL-16)发挥作用的分子机制。对182例ICH患者进行基因分型,分别为CC型(两条染色体均为胞嘧啶)、CT型(两条染色体均为两种变体)和TT型(两条染色体均为胸腺嘧啶),并计算其Kaplan-Meier生存曲线。此外,使用计算分析、荧光素酶测定和蛋白质印迹分析研究了miR-143与TLR2/IL-16之间可能的调控关系。此外,还比较了从受试者收集的脑脊液(CSF)和血清样本的炎症谱。基因分型为TT型的患者生存率最低,而基因分型为CC型的患者生存率最高。TLR2 mRNA被确定为miR-143的潜在靶点,而IL-16与miR-143无直接相互作用。使用转染了miR-143前体或TLR2小干扰RNA的细胞进一步研究了上述调控关系。此外,在从基因分型为TT型的患者收集的CSF/血清样本中,肿瘤坏死因子α、干扰素、IL-6、IL-10和NF-L-6等炎症因子表达水平最高,而在基因分型为CC型的患者中最低。相比之下,miR-143的表达水平与上述炎症因子的表达呈相反趋势。位于miR-143启动子区域的rs41291957 SNP降低了miR-143的表达,并上调了促炎因子TLR2的表达,最终导致ICH患者预后较差。