Low miR-1290 Levels Predict Sepsis Severity and Mortality

Researchers at Renmin Hospital of Wuhan University have identified a specific microRNA, designated miR-1290, as a potential diagnostic and prognostic biomarker for sepsis. The study, published in BMC Immunology, demonstrates that serum levels of miR-1290 are significantly downregulated in patients with sepsis compared to healthy controls. This reduction in expression correlates with increased disease severity and higher short-term mortality rates, suggesting that miR-1290 could serve as a reliable indicator for early risk stratification in clinical settings.

Sepsis is a life-threatening condition characterized by an aberrant host response to infection, leading to organ dysfunction and high mortality. Despite advances in medical technology, the prognosis for many patients remains unsatisfactory due to factors such as antibiotic resistance and individual heterogeneity in immune responses. The pathological mechanisms of sepsis involve complex processes including inflammatory storms, immune disturbance, and cell apoptosis. Consequently, identifying sensitive and reliable molecular biomarkers for early identification and prognostic prediction holds significant practical value for improving clinical risk classification and exploring novel therapeutic targets.

The study enrolled 127 healthy individuals as controls and 133 patients diagnosed with sepsis. Sepsis was diagnosed according to the International Consensus on Sepsis and Septic Shock, third edition. Inclusion criteria required patients to be at least 18 years old with full clinical records. Exclusion criteria included immunodeficiency status, ongoing treatment with immunosuppressants or glucocorticoids, presence of malignant tumors or severe chronic diseases, pregnancy or lactation, and history of recent surgery, trauma, or local infection within the past four weeks. All participants provided written informed consent, and the study was approved by the Ethics Committee of Renmin Hospital of Wuhan University.

To assess the diagnostic value of miR-1290, the researchers measured serum levels using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The results indicated that the relative expression level of serum miR-1290 was significantly lower in patients with sepsis than in the control group. Receiver operating characteristic (ROC) curve analysis yielded an area under the curve (AUC) of 0.870 for miR-1290 in the diagnosis of sepsis, with a 95% confidence interval of 0.826 to 0.913. The optimal cut-off value was determined to be 0.785, at which the sensitivity was 84.96% and the specificity was 76.38%. Logistic regression analysis further demonstrated that serum miR-1290 levels were independently associated with the onset of sepsis, alongside traditional markers such as albumin, white blood cell count, C-reactive protein, and procalcitonin.

The study also examined the correlation between miR-1290 expression and disease severity. In patients with sepsis, serum miR-1290 levels showed a strong negative correlation with the Sequential Organ Failure Assessment (SOFA) score and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Specifically, the correlation coefficient with the SOFA score was -0.710, and with the APACHE II score was -0.694, both with P values less than 0.001. These findings indicate that lower levels of miR-1290 are associated with more severe organ dysfunction and higher physiological derangement in septic patients.

For prognostic evaluation, the researchers followed all 133 sepsis patients for 28 days after admission to record survival status. The cohort included 92 survivors and 41 non-survivors. Serum miR-1290 levels were significantly decreased in survivors compared to non-survivors. ROC curve analysis revealed that miR-1290 had favorable prognostic value for predicting 28-day mortality, with an AUC of 0.818 and a 95% confidence interval of 0.747 to 0.895. The optimal cut-off value for mortality prediction was determined to be less than 0.565, with a sensitivity of 78.05% and a specificity of 70.65%. Kaplan-Meier analysis showed that patients with low miR-1290 expression had a markedly worse 28-day survival rate compared to those with high expression.

Cox regression analysis identified serum miR-1290 expression as an independent risk factor for 28-day mortality in patients with sepsis. The hazard ratio for miR-1290 was 0.296, with a 95% confidence interval of 0.140 to 0.626 and a P value of 0.001. This suggests that higher levels of miR-1290 are associated with a lower risk of death within the first 28 days. Other independent risk factors included the SOFA score and APACHE II score, while age and gender did not show statistically significant associations with mortality in this cohort.

To investigate the molecular mechanism underlying the protective role of miR-1290, the researchers established an in vitro inflammation model using THP-1 cells, a human monocytic leukemia cell line commonly used to model macrophage responses in sepsis. The cells were differentiated into macrophage-like cells using phorbol 12-myristate 13-acetate (PMA) and then stimulated with lipopolysaccharide (LPS) to simulate sepsis-induced injury. Bioinformatic prediction using databases such as miRTarBase, TargetScan, and miRDB identified TAO Kinase 1 (TAOK1) as a potential target gene of miR-1290. Dual-luciferase reporter assays confirmed that miR-1290 directly binds to and regulates TAOK1.

In the LPS-induced macrophage model, overexpression of miR-1290 suppressed TAOK1 expression, elevated cell viability, and reduced the secretion of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). Additionally, miR-1290 overexpression inhibited M1 macrophage polarization, indicated by downregulation of inducible nitric oxide synthase (iNOS) and cluster of differentiation 86 (CD86), and enhanced M2 polarization, indicated by upregulation of cluster of differentiation 206 (CD206) and arginase-1 (Arg-1). These changes suggest that miR-1290 promotes a shift from a pro-inflammatory to an anti-inflammatory and reparative macrophage phenotype.

Rescue experiments demonstrated that overexpression of TAOK1 reversed the anti-inflammatory and protective effects of miR-1290. When TAOK1 was overexpressed in the presence of miR-1290, the suppression of inflammatory cytokines and the promotion of cell viability were abolished. This confirms that the protective function of miR-1290 is partially dependent on its targeted inhibition of TAOK1. In clinical samples, TAOK1 levels were significantly elevated in patients with sepsis compared to healthy controls and showed a significant inverse association with miR-1290 expression. Furthermore, TAOK1 expression was higher in sepsis non-survivors than in survivors, reinforcing the link between the miR-1290/TAOK1 axis and disease outcomes.

The study acknowledges several limitations. The in vitro validation was conducted exclusively using THP-1-derived macrophages, which, while a standard model, cannot fully reflect the complex immune network involving multiple cell types such as neutrophils, T cells, and endothelial cells. The study lacked animal model validation, which limits the ability to fully simulate the dynamic pathological processes of sepsis in vivo. Additionally, the clinical cohort was relatively modest in size and recruited from a single institution, which may restrict the generalizability of the findings. Future studies are warranted to validate the clinical value of miR-1290 in large-scale, multicenter prospective trials and to further elucidate the cell-type-specific functions of the miR-1290/TAOK1 axis using co-culture and animal models.

Despite these limitations, the findings provide a novel candidate biomarker for the diagnosis and prognostic assessment of sepsis. The downregulation of miR-1290 in sepsis patients, its correlation with disease severity, and its predictive value for short-term mortality highlight its potential utility in clinical practice. By targeting TAOK1, miR-1290 exerts anti-inflammatory and protective effects on macrophages, offering a promising candidate target for therapeutic intervention. This study contributes to the growing body of evidence supporting the role of microRNAs in sepsis pathophysiology and underscores the importance of molecular biomarkers in improving patient outcomes.

Subject of Research: Diagnostic and prognostic value of miR-1290 in sepsis and its mechanism via TAOK1 targeting

Article Title: Downregulated miR-1290 serves as a diagnostic and prognostic biomarker in sepsis and protects against inflammatory injury by targeting TAOK1

Article References: Gao, D., & Wang, M. (2026). Downregulated miR-1290 serves as a diagnostic and prognostic biomarker in sepsis and protects against inflammatory injury by targeting TAOK1. BMC Immunology, 27(1), Article 97. https://doi.org/10.1186/s12865-026-00878-w

Image Credits: AI Generated

DOI: 10.1186/s12865-026-00878-w

Keywords: sepsis, miR-1290, biomarker, TAOK1, macrophage, prognosis, inflammation, diagnosis, Downregulated, serves, diagnostic, prognostic