miR-4772-3p通过靶向CISD2，成为脓毒性急性肾损伤的潜在诊断和预后生物标志物
miR-4772-3p serves as a potential diagnostic and prognostic biomarker in septic acute kidney injury by targeting CISD2.
摘要(中文译文)
本研究旨在探讨miR-4772-3p在脓毒症急性肾损伤（AKI）中的临床价值及作用。共纳入99例未发生AKI的脓毒症患者和93例发生AKI的脓毒症患者。采用RT-qPCR检测miR-4772-3p的表达。通过ROC曲线和logistic回归评估其诊断及预测价值，通过Kaplan-Meier法和Cox回归评估其预后价值。建立脂多糖（LPS）诱导的人肾小管上皮细胞（HK-2）模型，采用CCK-8评估细胞活力，流式细胞术检测细胞凋亡，ELISA检测炎性细胞因子（肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）），并检测氧化应激指标（超氧化物歧化酶（SOD）和丙二醛（MDA））。通过生物信息学和双荧光素酶实验鉴定miR-4772-3p的靶基因。miR-4772-3p在脓毒症AKI中表达上调，其水平与胱抑素C（Cys-C）、血清肌酐（Scr）、序贯器官衰竭评估（SOFA）评分、急性生理学与慢性健康状况评估II（APACHE II）评分、血尿素氮（BUN）及估算肾小球滤过率（eGFR）呈正相关。miR-4772-3p具有较高的诊断价值，是AKI发生的独立危险因素。此外，miR-4772-3p高表达与死亡率升高相关，可作为独立预后危险因素。在LPS诱导的HK-2模型中，观察到细胞活力下降、凋亡增加、促炎细胞因子（TNF-α、IL-6、IL-1β）升高、SOD活性降低及MDA含量增加。抑制miR-4772-3p可逆转上述损伤表型。机制上，CDGSH铁硫结构域蛋白2（CISD2）被证实为miR-4772-3p的直接靶基因；敲低CISD2可逆转抑制miR-4772-3p在病理调控中的作用。miR-4772-3p可能作为脓毒症AKI的潜在诊断和预后生物标志物。其上调可能通过调控CISD2促进脓毒症诱导的HK-2细胞损伤，从而促进AKI进展。
Abstract
This study aims to explore the clinical value and function of miR-4772-3p in septic acute kidney injury (AKI). A total of 99 septic patients without AKI and 93 with AKI were enrolled. RT-qPCR measured miR-4772-3p expression. Diagnostic and predictive value was assessed using the ROC curve and logistic regression, and prognostic utility was evaluated by Kaplan-Meier and Cox regression. An lipopolysaccharide (LPS)-induced human kidney‑2 cell line (HK-2) cell model was established to assess viability by CCK-8, apoptosis by flow cytometry, inflammatory cytokines (tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6), interleukin‑1β (IL‑1β)) by ELISA, and oxidative stress (superoxide dismutase (SOD) and malondialdehyde (MDA)). Bioinformatics and dual-luciferase assay identified the targets of miR-4772-3p. miR‑4772‑3p was upregulated in septic AKI, and its level positively correlated with cystatin C (Cys‑C), serum creatinine (Scr), Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood urea nitrogen (BUN), and estimated glomerular filtration rate (eGFR). miR‑4772‑3p showed high diagnostic value and was an independent risk factor for AKI occurrence. Moreover, higher miR‑4772‑3p expression was linked to elevated mortality and served as an independent prognostic risk factor. In the LPS‑induced HK‑2 model, decreased cell viability, increased apoptosis, elevated pro‑inflammatory cytokines (TNF-α, IL-6, IL-1β), reduced SOD activity, and increased MDA content were observed. Inhibition of miR‑4772‑3p reversed these injury phenotypes. Mechanistically, CDGSH iron sulfur domain 2 (CISD2) was verified as a direct target gene of miR‑4772‑3p; knockdown of CISD2 could reverse the effects of miR-4772-3p inhibition in pathological regulation. miR‑4772‑3p may serve as a potential diagnostic and prognostic biomarker for septic AKI. Its upregulation may promote sepsis-induced HK-2 cell injury by regulating CISD2, thereby facilitating AKI progression.
如何引用
AMA
Qiang Chen, Gaoshang Zhu. miR-4772-3p serves as a potential diagnostic and prognostic biomarker in septic acute kidney injury by targeting CISD2.. Renal failure. 2026; doi:10.1080/0886022X.2026.2665541.
APA
Qiang Chen, Gaoshang Zhu (2026). miR-4772-3p serves as a potential diagnostic and prognostic biomarker in septic acute kidney injury by targeting CISD2.. Renal failure. https://doi.org/10.1080/0886022X.2026.2665541
GB/T 7714
Qiang Chen, Gaoshang Zhu. miR-4772-3p serves as a potential diagnostic and prognostic biomarker in septic acute kidney injury by targeting CISD2.[J]. Renal failure, 2026 doi:10.1080/0886022X.2026.2665541.
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