Supplementary Material for: miR-874-3p is identified as a biomarker for acute kidney injury and mediates disease development via targeting MSRB3

Introduction: Acute kidney injury (AKI) is a common clinical disease, especially in the intensive care unit. Identification of reliable biomarker is of great clinical significance and benefit the therapy and prevention of AKI. The clinical significance and function of miR-874-3p in AKI development were evaluated in this study aiming to explore a novel biomarker for AKI. Methods: There were 83 AKI patients and 56 healthy individuals included and the serum samples were collected. The AKI animal models were established via ischemic/reperfusion and LPS on C57BL/6 mice. The expression of miR-874-3p was evaluated using PCR, while the potential downstream targets were also validated in AKI mice. Results: miR-874-3p was downregulated in both AKI patients and established AKI mice models. The downregulation of miR-874-3p could discriminate against AKI patients and predict poor prognosis of patients. miR-874-3p was negatively correlated with the levels of Scr, BUN, CRP, NEU, and PCT and positively correlated with the eGFR of AKI patients. In I/R- and LPS-induced AKI mice, overexpressing miR-874-3p could alleviate renal dysfunction, oxidative stress, and inflammation induced by AKI. Additionally, miR-874-3p could negatively regulate the expression of MSRB3, which was speculated as the potential mechanism underlying the function of miR-874-3p in AKI. Conclusion: miR-874-3p served as a diagnostic and prognostic biomarker of AKI and mediate the severity and development of AKI via targeting MSRB3.

引言：急性肾损伤（Acute kidney injury, AKI）是一类常见临床疾病，尤其在重症监护病房中高发。筛选可靠的生物标志物对AKI的诊疗与预防具有重要临床价值。本研究旨在探索AKI的新型生物标志物，评估miR-874-3p在AKI发生发展中的临床意义与作用。

方法：本研究纳入83例AKI患者与56例健康个体，采集其血清样本。通过缺血再灌注（ischemic/reperfusion, I/R）与脂多糖（lipopolysaccharide, LPS）构建C57BL/6小鼠AKI模型。采用聚合酶链式反应（PCR）检测miR-874-3p的表达水平，并在AKI小鼠模型中验证其潜在下游靶标。

结果：miR-874-3p在AKI患者及构建的AKI小鼠模型中均呈低表达。miR-874-3p低表达可有效区分AKI患者，并可预测患者不良预后。miR-874-3p的表达水平与AKI患者的血清肌酐（Serum Creatinine, Scr）、尿素氮（Blood Urea Nitrogen, BUN）、C反应蛋白（C-reactive protein, CRP）、中性粒细胞（Neutrophil, NEU）及降钙素原（Procalcitonin, PCT）水平呈负相关，与估算肾小球滤过率（estimated Glomerular Filtration Rate, eGFR）呈正相关。在I/R及LPS诱导的AKI小鼠模型中，过表达miR-874-3p可缓解AKI引发的肾功能异常、氧化应激与炎症反应。此外，miR-874-3p可负调控MSRB3的表达，这一机制可能是miR-874-3p参与AKI调控的潜在分子通路。

结论：本研究表明，miR-874-3p可作为AKI的诊断与预后生物标志物，并通过靶向MSRB3介导AKI的病情严重程度与疾病进展。