Clinical value of serum miR-943 as a diagnostic and prognostic biomarker for acute cerebral infarction and its mechanism of action via targeting BDNF

IF 3.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Archives of biochemistry and biophysics Pub Date : 2026-01-01 Epub Date: 2025-10-28 DOI:10.1016/j.abb.2025.110667

Sheng Lin, Junbin Chen

{"title":"Clinical value of serum miR-943 as a diagnostic and prognostic biomarker for acute cerebral infarction and its mechanism of action via targeting BDNF","authors":"Sheng Lin, Junbin Chen","doi":"10.1016/j.abb.2025.110667","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Dysregulated microRNAs are implicated in the acute cerebral infarction (ACI) pathogenesis.</div></div><div><h3>Aim</h3><div>This study investigated the clinical significance and mechanisms of miR-943 in ACI.</div></div><div><h3>Methods</h3><div>Serum miR-943 levels were measured using RT-qPCR in 132 ACI patients and 135 healthy controls (HC). Diagnostic potential was evaluated by ROC analysis. Prognosis was assessed using 90-day mRS scores. Correlations with clinical parameters were analyzed using Pearson's/Spearman's tests. Multivariate logistic regression identified outcome predictors. Bioinformatic prediction and experimental validation (dual-luciferase, RIP assays) identified miR-943 targets. An OGD/R model in BV-2 microglia simulated ischemia-reperfusion. Effects of miR-943 inhibitors and si-BDNF on viability (CCK-8), apoptosis (flow cytometry), and inflammation (ELISA) were assessed.</div></div><div><h3>Results</h3><div>ACI patients exhibited significantly elevated serum miR-943 expression and reduced BDNF levels versus HC. miR-943 showed high diagnostic value (AUC = 0.909, sensitivity 85.6 %, specificity 83.7 %). MiR-943 expression correlated positively with SBP, DBP, FBG, Hcy, NIHSS score, and infarct volume. Patients with a poor prognosis exhibited significantly higher miR-943 expression levels. Multivariate analysis identified high expression of miR-943 as an independent risk factor for poor outcome. BDNF was validated as a direct miR-943 target gene. OGD/R increased miR-943 expression, suppressed proliferation, promoted apoptosis, and enhanced the expression of inflammatory factors in BV-2 cells. Inhibiting miR-943 expression reversed these detrimental effects, enhancing proliferation and reducing apoptosis/inflammation. Critically, BDNF knockdown abolished the protective effects of miR-943 inhibition.</div></div><div><h3>Conclusion</h3><div>Serum miR-943 is a promising diagnostic and prognostic biomarker for ACI. It exerts pathological effects by post-transcriptionally suppressing BDNF. Targeting the miR-943/BDNF axis represents a potential therapeutic strategy.</div></div>","PeriodicalId":8174,"journal":{"name":"Archives of biochemistry and biophysics","volume":"775 ","pages":"Article 110667"},"PeriodicalIF":3.5000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of biochemistry and biophysics","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003986125003819","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/10/28 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Dysregulated microRNAs are implicated in the acute cerebral infarction (ACI) pathogenesis.

Aim

This study investigated the clinical significance and mechanisms of miR-943 in ACI.

Methods

Serum miR-943 levels were measured using RT-qPCR in 132 ACI patients and 135 healthy controls (HC). Diagnostic potential was evaluated by ROC analysis. Prognosis was assessed using 90-day mRS scores. Correlations with clinical parameters were analyzed using Pearson's/Spearman's tests. Multivariate logistic regression identified outcome predictors. Bioinformatic prediction and experimental validation (dual-luciferase, RIP assays) identified miR-943 targets. An OGD/R model in BV-2 microglia simulated ischemia-reperfusion. Effects of miR-943 inhibitors and si-BDNF on viability (CCK-8), apoptosis (flow cytometry), and inflammation (ELISA) were assessed.

Results

ACI patients exhibited significantly elevated serum miR-943 expression and reduced BDNF levels versus HC. miR-943 showed high diagnostic value (AUC = 0.909, sensitivity 85.6 %, specificity 83.7 %). MiR-943 expression correlated positively with SBP, DBP, FBG, Hcy, NIHSS score, and infarct volume. Patients with a poor prognosis exhibited significantly higher miR-943 expression levels. Multivariate analysis identified high expression of miR-943 as an independent risk factor for poor outcome. BDNF was validated as a direct miR-943 target gene. OGD/R increased miR-943 expression, suppressed proliferation, promoted apoptosis, and enhanced the expression of inflammatory factors in BV-2 cells. Inhibiting miR-943 expression reversed these detrimental effects, enhancing proliferation and reducing apoptosis/inflammation. Critically, BDNF knockdown abolished the protective effects of miR-943 inhibition.

Conclusion

Serum miR-943 is a promising diagnostic and prognostic biomarker for ACI. It exerts pathological effects by post-transcriptionally suppressing BDNF. Targeting the miR-943/BDNF axis represents a potential therapeutic strategy.

Abstract Image

查看原文本刊更多论文

血清miR-943作为急性脑梗死诊断和预后生物标志物的临床价值及其靶向BDNF的作用机制

背景：microrna失调与急性脑梗死（ACI）的发病机制有关。目的：探讨miR-943在ACI中的临床意义及机制。方法：采用RT-qPCR检测132例ACI患者和135例健康对照（HC）的血清miR-943水平。采用ROC分析评估诊断潜力。采用90天mRS评分评估预后。使用Pearson’s/Spearman’s检验分析与临床参数的相关性。多变量逻辑回归确定了结果预测因子。生物信息学预测和实验验证（双荧光素酶，RIP测定）确定了miR-943靶点。BV-2小胶质细胞OGD/R模型模拟缺血再灌注。评估miR-943抑制剂和si-BDNF对细胞活力（CCK-8）、细胞凋亡（流式细胞术）和炎症（ELISA）的影响。结果：与HC相比，ACI患者血清miR-943表达显著升高，BDNF水平显著降低。miR-943具有较高的诊断价值（AUC=0.909，敏感性85.6%，特异性83.7%）。MiR-943的表达与收缩压、舒张压、空腹血糖、Hcy、NIHSS评分和梗死体积呈正相关。预后较差的患者miR-943表达水平明显升高。多因素分析发现miR-943的高表达是不良预后的独立危险因素。BDNF被证实是miR-943的直接靶基因。OGD/R增加BV-2细胞中miR-943的表达，抑制细胞增殖，促进细胞凋亡，增强炎症因子的表达。抑制miR-943的表达逆转了这些不利影响，增强了细胞增殖，减少了细胞凋亡/炎症。关键的是，BDNF敲低消除了miR-943抑制的保护作用。结论：血清miR-943是一种有前景的ACI诊断和预后生物标志物。它通过转录后抑制BDNF发挥病理作用。靶向miR-943/BDNF轴代表了一种潜在的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Archives of biochemistry and biophysics 生物-生化与分子生物学

CiteScore

7.40

自引率

0.00%

发文量

245

审稿时长

26 days

期刊介绍： Archives of Biochemistry and Biophysics publishes quality original articles and reviews in the developing areas of biochemistry and biophysics. Research Areas Include: • Enzyme and protein structure, function, regulation. Folding, turnover, and post-translational processing • Biological oxidations, free radical reactions, redox signaling, oxygenases, P450 reactions • Signal transduction, receptors, membrane transport, intracellular signals. Cellular and integrated metabolism.