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

Abstract

Background

MicroRNAs (miRNAs) are key regulators and potential biomarkers for early diagnosis and prognosis of sepsis. To investigate the diagnostic and prognostic value, and molecular mechanism of miR-1290 in sepsis.

Methods

Enrollment comprised 127 healthy controls and 133 patients with sepsis. RT‑qPCR measured serum miR-1290 and TAO Kinase 1 (TAOK1) levels. ROC curve and Logistic regression assessed diagnostic efficacy and risk prediction of miR-1290 for sepsis. Kaplan-Meier and Cox regression evaluated its short-term prognostic value. An LPS-induced macrophage (THP-1) inflammation model was established to examine the effects of miR-1290 on cell viability (CCK-8), inflammatory cytokines TNF-α, IL-6, and IL-1β (ELISA), and macrophage polarization markers (RT-qPCR). Bioinformatic prediction and dual-luciferase reporter verified the interaction between miR-1290 and TAOK1, and rescue experiments were conducted to determine that TAOK1 reverses the biological functions of miR-1290.

Results

miR-1290 was downregulated in patients with sepsis and showed high diagnostic value. Its expression level was negatively correlated with both SOFA and APACHE II scores, and demonstrated good predictive performance for short-term mortality. In the LPS-induced macrophage model, overexpression of miR-1290 suppressed TAOK1 expression, elevated cell viability, suppressed the secretion of TNF-α, IL-6, and IL-1β, inhibited M1 polarization (downregulation of iNOS and CD86), and enhanced M2 polarization (upregulation of CD206 and Arg-1). Moreover, TAOK1 overexpression reversed the anti-inflammatory and protective effects of miR-1290.

Conclusions

Downregulated miR-1290 shows potential as both a diagnostic and prognostic indicator in sepsis. It may exert a protective effect on macrophages by targeting TAOK1, thereby inhibiting disease progression.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12865-026-00878-w.

Introduction

Sepsis, a systemic inflammatory condition arising from an aberrant host response to infection, represents one of the most prevalent and critical acute severe illnesses in clinical practice, marked by increased mortality, substantial disability risks, and heavy medical financial costs [1]. The systemic inflammatory response induced by sepsis presents a cascade amplification effect, causing severe damage to multiple tissues and organs throughout the body, with chills, fever, and palpitations as its typical clinical manifestations [2]. Despite continuous advances in medical technology and theoretical understanding, as well as optimized therapeutic strategies for sepsis, the growing prevalence of pathogenic bacterial drug resistance and marked individual heterogeneity in immune responses among patients still lead to progression into septic shock and multiple organ failure in a large number of cases, resulting in an unsatisfactory overall prognosis [3]. In addition, the pathological mechanism of sepsis involves multiple complex processes, including inflammatory storm, immune disturbance, and cell apoptosis, and specific therapeutic targets and precise intervention strategies are still lacking at present [4]. Therefore, screening sensitive and reliable biomarkers at the molecular level for early identification and prognostic prediction of sepsis, as well as elucidating the regulatory mechanism of key molecules, holds practical value for improving the clinical risk classification system and exploring novel therapeutic targets.

Endogenous, conserved, non-coding small RNAs known as microRNAs (miRNAs) regulate gene expression post-transcriptionally mainly through binding to the 3′-UTR of target genes. They extensively participate in various biological activities, including inflammatory activation, immune cell polarization, cell proliferation and apoptosis, and signal transduction [5]. Currently, miRNAs are widely researched across a range of inflammatory disorders, acute critical illnesses, and metabolic disorders. In the sepsis field, miR-223 exerts a protective role by reducing lymphocyte apoptosis and promoting lymphocyte proliferation, and it is associated with reduced sequential organ failure assessment (SOFA) scores and higher survival rates [6]. miR-106a-5p alleviates macrophage pyroptosis and inflammatory responses by targeting and inhibiting PFKFB3-mediated glycolysis, thereby playing a protective role in sepsis [7]. Inhibition of miR-135a reduces lipopolysaccharide (LPS)-induced human monocytic leukemia line (THP-1) cell injury through targeted regulation of MYOM1, providing a potential molecular target for sepsis [8]. Together, these findings indicate that miRNAs participate in the occurrence and progression of sepsis from multiple dimensions, such as immune homeostasis and inflammatory injury, by targeting downstream key genes, representing an important research direction for the discovery of novel biomarkers and therapeutic targets for sepsis.

miR-1290 is a miRNA that exerts pivotal regulatory roles in a variety of human diseases [9]. It has been validated to participate in the pathological progression of multiple inflammation-associated disorders and modulate inflammatory cytokine secretion as well as cellular functional remodeling. For instance, miR-1290 binds to MYLK in a targeted manner and suppresses its expression, thereby alleviating pulmonary endothelial barrier dysfunction induced by tumor necrosis factor‑α (TNF‑α), LPS, and mechanical stress [10]. Plasma miR-1290 acts as a specific biomarker for necrotizing enterocolitis to assist clinical decision-making [11]. In the context of sepsis, miR-1290 is regulated by long non‑coding RNA (lncRNA) RP11-510J16.3; it can attenuate cell pyroptosis, keep the blood-brain barrier intact, and further relieve neuroinflammation and cognitive impairment in sepsis-associated encephalopathy (SAE) [12]. Moreover, miR-1290 is markedly downregulated in sepsis, as one of the differentially expressed miRNAs, it may participate in immune imbalance underlying sepsis and related lung injury via modulating its target genes [13]. Nevertheless, the exact expression profile, clinical relevance, and molecular basis of miR-1290 in sepsis remain incompletely clarified. Based on this, the present study hypothesized that miR-1290 is differentially expressed in sepsis and may exert important biological functions. To test this hypothesis, this study enrolled patients with sepsis and healthy controls to detect the differential expression of serum miR-1290 and analyze its clinical implications. Meanwhile, an in vitro cellular inflammation model was conducted to investigate the regulatory function of miR-1290, aiming to systematically elaborate on the biological role and mechanistic basis of miR-1290 in sepsis.

Materials and methods

Patient enrollment and sample collection

This study included 127 healthy individuals as controls and 133 patients with sepsis. The Ethics Committee of Renmin Hospital of Wuhan University approved this study. All methods were performed in accordance with relevant guidelines, regulations, and the Declaration of Helsinki. Written informed consent was collected from all participants.

Sepsis was diagnosed according to the International Consensus on Sepsis and Septic Shock, third edition [14]. Inclusion criteria: (1) patients with full clinical records; (2) age ≥ 18 years old. Exclusion criteria: (1) presence of immunodeficiency status (including HIV positivity); (2) ongoing treatment with immunosuppressants, glucocorticoids, or radiotherapy; (3) complicated with malignant tumors or severe chronic diseases; (4) females during pregnancy or lactation; (5) history of recent surgery, trauma, or local infection within the past 4 weeks.

Fasting peripheral venous blood was drawn from all subjects within 24 h after admission. After centrifugation at 3000 r/min for 15 min, serum was separated and frozen at -80 °C for subsequent detection.

All enrolled patients with sepsis were followed up for 28 days after admission, and their survival status was recorded accordingly.

Cell culture

THP-1 cells were obtained from the American Type Culture Collection (ATCC, USA). They were maintained in RPMI-1640 medium (Gibco, USA) supplemented with 10% fetal bovine serum (Sigma Aldrich, USA) and 1% penicillin-streptomycin (Invitrogen, USA), and incubated at 37 °C in a 5% CO₂ constant-temperature incubator.

Cell transfection

miR-1290 mimic (mimic-miR) and its control (mimic-NC), together with TAO Kinase 1 (TAOK1) overexpression plasmid (OE-TAOK1) and its control (OE-NC), were obtained from GenePharma Company (Shanghai, China). Lipofectamine 3000 (Invitrogen, USA) was used for cell transfection, strictly following the manufacturer’s protocol.

Cell treatment

To model sepsis-induced injury in vitro, THP-1 cells were first differentiated into M0-phenotype macrophage-like cells using 100 nM phorbol 12-myristate 13-acetate (PMA) for 24 h, followed by stimulation with 1 µg/mL LPS for an additional 24 h [15].

RNA extraction and RT-qPCR

TRIzol reagent was used to isolate total RNA from serum samples and cells separately. Reverse transcription was performed with iScript cDNA Synthesis Kit (Bio-Rad, USA) and miRNA Reverse Transcription Kit (Ribobio, Guangzhou) to convert RNA to cDNA. qPCR was run with GoTaq qPCR Master Mix (Promega, USA) on a real-time system. The qPCR reaction mixture (20 µL) consisted of 10 µL of GoTaq qPCR Master Mix, 0.5 µM of each forward and reverse primer, 2 µL of cDNA, and nuclease‑free water to 20 µL. The thermal cycling conditions were as follows: initial denaturation at 95 °C for 3 min, followed by 40 cycles of 95 °C for 15 s, 60 °C for 30 s, and 72 °C for 30 s, with a final extension at 72 °C for 5 min. U6 and GAPDH were internal references, and the relative expression levels of target genes were calculated via the 2^-ΔΔCt method. The primer sequences used are as shown in Supplementary Table 1.

Cell counting kit-8 (CCK-8) assay

Cell viability after different treatments was evaluated by the CCK-8 assay kit (Solarbio, Beijing). After experimental treatment, cells were incubated for 24, 48, and 72 h. Subsequently, each well received 10 µL of CCK-8 reagent, followed by a 2-h incubation at 37 °C/5% CO₂. The optical density at 450 nm was measured with a Bio-Rad microplate reader (Bio-Rad, USA).

Enzyme-linked immunosorbent assay (ELISA)

The levels of TNF-α, interleukin-1β (IL-1β), and interleukin-6 (IL-6) in cell culture supernatants were detected by ELISA kits (Mlbio, Shanghai). Before detection, cell supernatants were spun at 3000 r/min for 15 min, and the subsequent measurement was carried out following the manufacturer’s manual.

Dual-luciferase reporter assays

Downstream target genes of miR-1290 were predicted using the miRTarBase (https://mirtarbase.cuhk.edu.cn/~miRTarBase/miRTarBase_2025/php/index.php), TargetScan (https://www.targetscan.org/vert_80/), and miRDB (https://mirdb.org/) databases. The TAOK1 wild-type (TAOK1-WT) and mutant (TAOK1-MUT) fragments harboring the predicted miR-1290 binding site were cloned into pmirGLO (Promega, USA) to create reporter plasmids. Cells were co-transfected with each plasmid plus miR-1290 mimic, inhibitor, or matched controls using Lipofectamine 3000. After 48 h, luciferase activity was measured via the Dual-Luciferase Assay kit (Promega, USA), with firefly activity normalized to Renilla activity.

Statistical analysis

SPSS 23.0 and GraphPad Prism 10.1 were used for statistical analysis. Chi-square tested categorical differences; t-test (two groups) and one-way ANOVA (followed by Tukey’s post hoc test for multiple comparisons) were used for continuous variables. Pearson correlation assessed relationships between variables. The diagnostic and predictive performance of miR-1290 in sepsis was evaluated using ROC curves and Logistic regression. Prognostic value was assessed by Kaplan-Meier curves and Cox regression. All in vitro cellular experiments were performed with four independent biological replicates (n = 4).

Results

Expression and clinical significance of miR-1290 in Sepsis

No marked disparities in baseline demographic and clinical characteristics between the healthy control group and patients with sepsis, including age, gender, body mass index (BMI), smoking history, drinking history, hypertension, hyperlipidemia, diabetes history, and serum creatinine (Scr), all P > 0.05, indicating well-matched baseline data between the two cohorts. Relative to controls, white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) levels were markedly elevated in patients with sepsis (all P < 0.001), while serum albumin content was significantly decreased (P < 0.001; Table 1). Clinical sample detection results highlighted that the relative expression level of serum miR-1290 was significantly downregulated in patients with sepsis compared with the control group (Fig. 1A).

Table 1.

Comparison of baseline data of controls and patients with sepsis

Features	Controls (n = 127)	Sepsis (n = 133)	P value
Age (years)	54.80 ± 10.26	55.14 ± 11.15	0.799
Gender (male/%)	68 (53.54)	74 (55.64)	0.803
BMI (kg/m2)	23.87 ± 2.97	24.16 ± 3.41	0.467
Smoking (yes/%)	54 (42.52)	58 (43.61)	0.901
Drinking (yes/%)	58 (45.67)	63 (47.37)	0.805
Hypertension (yes/%)	41 (32.28)	45 (33.83)	0.794
Hyperlipidemia (yes/%)	45 (35.43)	51 (38.35)	0.700
Diabetes (yes/%)	43 (33.86)	44 (33.08)	0.896
Scr (mg/dL)	0.93 ± 0.31	1.03 ± 0.47	0.051
Albumin (g/L)	44.30 ± 6.93	30.34 ± 5.57	< 0.001
WBC (× 109/L)	7.21 ± 1.50	13.89 ± 5.09	< 0.001
CRP (mg/L)	5.80 ± 1.60	102.36 ± 23.85	< 0.001
PCT (ng/mL)	0.11 ± 0.04	5.12 ± 1.99	< 0.001
SOFA score		6.19 ± 2.15
APACHE II score		12.98 ± 4.87

BMI body mass index, Scr Serum creatinine, WBC White blood cell, CRP C-reactive protein, PCT procalcitonin, SOFA Sequential organ failure assessment, APACHE II Acute physiology and chronic health evaluation II

Bold font indicates statistically significant differences

Fig. 1.

Diagnostic value of miR-1290 and its correlation with disease severity insepsis.A Comparison of serum miR-1290 expression between healthy controls and patients with sepsis. B ROC curve of serum miR-1290 for the diagnosis of sepsis. C Correlation between miR-1290 expression and SOFA score. D Correlation between miR-1290 expression and APACHE Ⅱ score. (***P < 0.001)

The ROC curve yielded an AUC of 0.870 for miR-1290 in the diagnosis of sepsis (95% CI: 0.826–0.913, P < 0.001). The optimal cut‑off value was determined as 0.785, at which the sensitivity was 84.96%, specificity 76.38%, and the Youden index 0.613 (Fig. 1B). Logistic regression further demonstrated that Albumin (OR = 0.569, 95% CI: 0.331–0.978, P = 0.041), WBC (OR = 1.783, 95% CI: 1.044–3.045, P = 0.034), CRP (OR = 1.884, 95% CI: 1.090–3.255, P = 0.023), PCT (OR = 1.944, 95% CI: 1.122–3.370, P = 0.018), and serum miR-1290 (OR = 0.339, 95% CI: 0.195–0.588, P < 0.001) were associated with the onset of sepsis. By contrast, other indicators showed no statistically significant correlation (Table 2).

Table 2.

Logistic regression analysis of risk factors for the occurrence of sepsis

Features	OR	95% CI	P value
Age	1.046	0.607–1.803	0.871
Gender	1.003	0.563–1.789	0.991
BMI	1.045	0.607–1.797	0.874
Smoking	1.178	0.677–2.052	0.562
Drinking	1.188	0.689–2.048	0.536
Hypertension	1.355	0.788–2.331	0.272
Hyperlipidemia	1.394	0.786–2.471	0.256
Diabetes	1.401	0.781–2.511	0.258
Scr	1.494	0.863–2.583	0.151
Albumin	0.569	0.331–0.978	0.041
WBC	1.783	1.044–3.045	0.034
CRP	1.884	1.090–3.255	0.023
PCT	1.944	1.122–3.370	0.018
miR-1290	0.339	0.195–0.588	< 0.001

BMI body mass index, Scr Serum creatinine, WBC White blood cell, CRP C-reactive protein, PCT procalcitonin

Bold font indicates statistically significant differences

Correlation analysis revealed that the serum level of miR-1290 in patients with sepsis was negatively correlated with the SOFA score (r=-0.710, P < 0.001; Fig. 1C) and the acute physiology and chronic health evaluation II (APACHE Ⅱ) score (r=-0.694, P < 0.001; Fig. 1D).

Prognostic value of miR-1290 in patients with sepsis

A total of 133 patients with sepsis were included in the 28‑day survival analysis, including 92 survivors and 41 non‑survivors. The serum level of miR-1290 was significantly decreased in survivors compared to non‑survivors (Fig. 2A). The ROC curve revealed that miR-1290 had a favorable prognostic value for mortality in patients with sepsis, with an AUC of 0.818 (95% CI: 0.747–0.895, P < 0.001). The optimal cut‑off value was determined as < 0.565, at which the sensitivity was 78.05%, specificity 70.65%, and the Youden index 0.487 (Fig. 2B). Patients with sepsis were categorized by mean miR-1290 into high-expression (n = 62) and low-expression (n = 71). Kaplan-Meier analysis revealed that patients with low miR-1290 had a markedly worse 28-day survival rate compared to those with high miR-1290 (Fig. 2C). Cox regression demonstrated that SOFA score (HR = 2.919, 95% CI: 1.077–4.461, P = 0.030), APACHE Ⅱ score (HR = 2.277, 95% CI: 1.148–4.516, P = 0.019) and serum miR-1290 expression level (HR = 0.296, 95% CI: 0.140–0.626, P = 0.001) were associated with the 28-day mortality of patients with sepsis, whereas other factors such as age and gender exhibited no statistical significance (Table 3).

Fig. 2.

Prognostic value of miR-1290 in patients with sepsis. A Serum miR-1290 expression levels in survivors and non-survivors with sepsis. B ROC curve of miR-1290 for predicting 28-day mortality in patients. C Kaplan-Meier survival curves of patients with different miR-1290 expression levels. (**P < 0.01)

Table 3.

Cox regression analysis of independent risk factors for 28-day mortality in patients with sepsis

Features	HR	95% CI	P value
Age	1.016	0.499–2.068	0.966
Gender	1.119	0.566–2.212	0.747
BMI	1.181	0.602–2.316	0.629
Smoking	1.203	0.615–2.353	0.589
Drinking	1.261	0.595–2.672	0.545
Hypertension	1.292	0.641–2.606	0.474
Hyperlipidemia	1.344	0.659–2.742	0.416
Diabetes	1.460	0.748–2.848	0.267
Scr	1.577	0.771–3.227	0.212
Albumin	0.682	0.351–4.123	0.261
WBC	1.873	0.875–4.011	0.106
CRP	1.985	0.956–4.123	0.066
PCT	1.950	0.983–3.868	0.056
SOFA score	2.919	1.077–4.461	0.030
APACHE II score	2.277	1.148–4.516	0.019
miR-1290	0.296	0.140–0.626	0.001

BMI body mass index, Scr Serum creatinine, WBC White blood cell, CRP C-reactive protein, PCT procalcitonin, SOFA Sequential organ failure assessment, APACHE II Acute physiology and chronic health evaluation II

Bold font indicates statistically significant differences

miR-1290 directly targets TAOK1

Cross-prediction was performed using three databases, including miRTarBase, TargetScan, and miRDB, and a total of seven potential common target genes of miR-1290 were screened out, including TAOK1, DKK3, EMP2, P2RY1, RORA, CLOCK, and SPARCL1 (Fig. 3A). qPCR verification results indicated that the level of TAOK1 was markedly downregulated after miR-1290 overexpression (Fig. 3B). Dual-luciferase experiments corroborated that miR-1290 could directly target TAOK1 (Fig. 3C). In the TAOK1 WT, overexpression of miR-1290 markedly inhibited luciferase activity, while miR-1290 inhibition significantly enhanced luciferase activity; however, such regulatory effects were abolished in the MUT (Fig. 3C).

Fig. 3.

miR-1290 targets and regulates TAOK1. A Venn diagram of potential miR-1290 target genes predicted by three databases. B Validation of the expression of potential target genes, n = 4. C Dual-luciferase reporter assay confirming the interaction between miR-1290 and TAOK1, n = 4. D TAOK1 mRNA expression levels in patients with sepsis and controls. E Correlation analysis between miR-1290 and TAOK1 expression. F TAOK1 expression levels in survivors and non-survivors with sepsis. (***P < 0.001, **P < 0.01)

Further verification of clinical samples showed that the level of TAOK1 in patients with sepsis was remarkably elevated relative to healthy controls (Fig. 3D). Correlation analysis revealed a significant inverse association between TAOK1 and miR-1290 expression in patients with sepsis (r = -0.713, P < 0.001; Fig. 3E). In addition, the expression level of TAOK1 was significantly elevated in sepsis non-survivors compared with survivors (Fig. 3F).

TAOK1 Overexpression Reverses the Effect of miR-1290 on Macrophages

qPCR results demonstrated that LPS treatment significantly suppressed the level of miR-1290 in cells, whereas transfection with miR-1290 mimic effectively reversed this trend (Fig. 4A). Meanwhile, LPS treatment markedly upregulated TAOK1 expression. Overexpression of miR-1290 inhibited TAOK1 expression, while co-transfection with the TAOK1 overexpression plasmid partially restored the expression level of TAOK1 (Fig. 4B). CCK-8 assays revealed that LPS treatment obviously inhibited cell viability. miR-1290 overexpression promoted cell viability under LPS stimulation, and this promotional effect was abolished by TAOK1 overexpression (Fig. 4C). ELISA and qPCR results revealed that LPS exposure remarkably facilitated the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β (Fig. 4D), upregulated the levels of pro-inflammatory macrophage markers (Fig. 4E), including inducible nitric oxide synthase (iNOS) and cluster of differentiation 86 (CD86), and downregulated the levels of anti-inflammatory markers (Fig. 4F), including cluster of differentiation 206 (CD206) and arginase‑1 (Arg‑1). miR-1290 overexpression significantly restrained the above pro-inflammatory responses and facilitated the transformation towards an anti-inflammatory phenotype, while TAOK1 overexpression further reversed the regulatory function of miR-1290.

Fig. 4.

miR-1290 regulates LPS-induced THP-1 cells via targeting TAOK1. A miR-1290 expression levels in each group. B Changes in TAOK1 expression in each group. C Proliferative activity of cells in each group was detected by CCK-8 assay. D Secretion levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) in cell culture supernatants were detected by ELISA. E Expression levels of pro-inflammatory macrophage markers (iNOS, CD86) in each group. F Expression levels of anti-inflammatory macrophage markers (CD206, Arg-1) in each group. (***P < 0.001, n = 4)

Discussion

Sepsis often leads to multiple organ dysfunction, and it progresses rapidly and carries a high mortality rate [16]. Early screening and diagnosis are critical for timely intervention. Current clinical tools include qSOFA, SOFA scores, and biomarkers such as PCT and CRP. However, these methods have limitations: insufficient sensitivity, suboptimal specificity, diagnostic delay, and lack of individualized assessment [3]. Owing to their high stability, convenient detection, and non-invasive nature, miRNAs have emerged as promising sepsis biomarkers [5]. In recent years, numerous studies have reported the roles of various miRNAs in sepsis. For instance, miR-145 negatively regulates the inflammatory response by targeting ADAM17, but no relevant clinical studies have been conducted [17]. miR-1290 has also been reported to be differentially expressed in sepsis-related organ dysfunction [12, 13], yet its exact role in sepsis remains poorly clarified. This study found that the serum level of miR-1290 in patients with sepsis was markedly lower compared to healthy controls. Marked disparities were observed in clinical indicators, including albumin, WBC, CRP, and PCT, between the two groups. As an indicator reflecting nutritional status and inflammatory response, albumin declines markedly in sepsis due to capillary leakage and reduced hepatic synthesis [18]. As a traditional infection marker, WBC may increase or decrease during sepsis [19]. CRP, an acute-phase protein produced by hepatocytes, is highly sensitive to infectious inflammation and can be applied for early screening and therapeutic efficacy evaluation of sepsis [20]. PCT is a relatively specific biomarker for bacterial infection, and its level is positively related to the severity and prognosis of sepsis [21]. Further ROC assessment demonstrated that miR-1290 could effectively distinguish patients with sepsis from healthy controls. Logistic regression analysis demonstrated that miR-1290, albumin, WBC, CRP, and PCT were all independent predictors of the occurrence of sepsis. Given that albumin, WBC, CRP, and PCT are well-recognized gold-standard biomarkers [20], this finding suggests that miR-1290 possesses considerable diagnostic and predictive value. In addition, the level of miR-1290 showed a strong inverse association with both SOFA and APACHE Ⅱ scores. The SOFA score objectively quantifies the degree of organ dysfunction by dynamically evaluating the functional status of six organ systems [22], while the APACHE Ⅱ score comprehensively assesses acute physiological parameters, age, and chronic health conditions [23]. These results indicate that miR-1290 is highly related to disease severity. The above findings suggest that the level of miR-1290 is of great significance for condition assessment in patients with sepsis, and can serve as a novel early warning indicator for early diagnosis and risk prediction. Meanwhile, miR-1290 expression can reflect the disease burden and organ injury severity of sepsis, providing a new theoretical rationale for clinical progression evaluation and therapeutic management.

Current core clinical interventions for patients with sepsis mainly consist of comprehensive strategies, including antibiotic therapy, fluid resuscitation, and vasoactive agents. However, clinical management still faces challenges such as antibiotic resistance, heterogeneous immune responses, and the absence of specific therapeutic targets, resulting in persistently poor patient prognosis [24]. In this study, patients with sepsis were subjected to a 28-day short-term follow-up. The data indicated that serum miR-1290 level was lower in non-survivors than in survivors. Survival curve and ROC confirmed that miR-1290 expression could effectively distinguish the 28-day survival status of patients with sepsis and exhibited favorable efficacy for short-term prognostic evaluation. Further Cox regression analysis revealed that miR-1290 expression, SOFA score, and APACHE Ⅱ score were all factors independently predicting 28-day mortality in sepsis. As classical clinical indicators for evaluating mortality risk in sepsis, SOFA and APACHE Ⅱ scores indicated that miR-1290 level was closely correlated with adverse prognosis of sepsis [22, 23]. The above findings suggest that miR-1290 holds potential as a molecular biomarker for prognostic stratification in patients with sepsis, enabling early identification of individuals at high mortality risk, and providing a novel evaluation indicator for early risk warning, dynamic disease monitoring, and refined clinical management of sepsis. Previous studies have identified miR‑625‑5p and miR‑10a as potential biomarkers for sepsis diagnosis and prognosis; miR‑1290 in this study shows a better diagnostic and predictive performance [25, 26].

Sepsis arises from an infection-induced, systemic, and dysregulated immune-inflammatory reaction, which ultimately leads to circulatory disturbance, metabolic disorders, and multiple organ failure. The THP-1 cell line is a commonly used human cell line for in vitro sepsis research [27]. LPS-stimulated THP-1 cells serve as a gold-standard human in vitro model for investigating sepsis-related inflammatory responses, immune regulation, and organ injury mechanisms, and can simulate macrophage activation and inflammatory reactions induced by infection. Previous studies have adopted LPS to activate differentiated THP-1 macrophages to verify the role of relevant molecules in sepsis [15]. In this study, after THP-1 cells were differentiated and induced by LPS, cell viability was markedly reduced, inflammatory cytokine concentrations were significantly elevated, the levels of M1 polarization markers (iNOS, CD86) were upregulated, and the levels of M2 polarization markers (CD206, Arg-1) were obviously downregulated. Among these indicators, cell viability reflects the survival and functional status of macrophages under septic conditions [26]; inflammatory cytokines, as core effector molecules, mediate systemic inflammation, vascular endothelial injury and multiple organ dysfunction [28]; M1 polarization markers are key molecules representing the classical pro-inflammatory polarization of macrophages and participate in pathogen clearance [29]; M2 polarization markers characterize the alternative activated or reparative phenotype transformation of macrophages, and are involved in inflammation resolution, tissue remodeling and immune regulation [16]. Changes in the above indicators collectively reveal that macrophages tend to shift toward the pro-inflammatory M1 phenotype while the anti-inflammatory reparative M2 phenotype is suppressed under septic conditions, thereby driving tissue damage and immune imbalance [29]. Under this pathological background, the level of miR-1290 was markedly reduced, which was consistent with the expression trend observed in clinical samples. Overexpression of miR-1290 could notably reverse the above phenotypic changes of macrophages induced by LPS, suggesting that miR-1290 may protect macrophages against LPS stimulation, enhance cell viability, inhibit inflammatory responses, promote functional transformation toward the M2 phenotype, and thereby restrain the progression of sepsis.

Mechanistically, this study confirmed that TAOK1 is a downstream target of miR-1290 through bioinformatics prediction and dual-luciferase reporter gene assays. TAOK1, belonging to the serine/threonine kinase family, has been shown to promote both the synthesis and secretion of pro-inflammatory cytokines and to be pivotal in sepsis [30–32]. Specifically, TAOK1 positively regulates TLR4-induced macrophage inflammation via the TAK1/TRAF6/TPL2 axis, boosting pro-inflammatory cytokines [30]. On the other hand, TAOK1 negatively regulates IL-17 signaling by blocking IL-17R-Act1 complex formation, thus reducing autoimmune inflammatory injury [31]. Furthermore, TAOK1 promotes apoptosis and barrier dysfunction in sepsis-associated intestinal epithelial cells via p38 MAPK activation [32]. In this study, serum TAOK1 level was upregulated in patients with sepsis and showed a marked negative correlation with miR-1290 expression. In the LPS-induced macrophage model, TAOK1 overexpression reversed the anti-inflammatory effect of miR-1290, further verifying that the protective function of miR-1290 is partially dependent on its targeted inhibition of TAOK1. Collectively, these observations reveal that miR-1290 may exert anti-inflammatory effects and regulate macrophage polarization in the LPS-induced cellular model of sepsis via targeted inhibition of TAOK1.

In the study, in vitro validation was exclusively conducted using THP-1-derived macrophages. While this model is capable of adequately recapitulating macrophage inflammatory responses during sepsis, the pathological progression of sepsis involves crosstalk among multiple cell types, including neutrophils, T cells, endothelial cells, and epithelial cells. As such, a single-cell-type culture model cannot fully reflect the complex immune network, which constitutes a limitation of the current work. Prior investigations have verified the function of relevant molecules in endothelial and epithelial cells [17, 33]. And this study was conducted only at the cellular level and lacks corresponding animal model studies, making it difficult to fully simulate the dynamic pathological processes of sepsis in vivo. Due to time and resource constraints, further validation using co‑culture systems or animal models was not performed in this study. Moreover, constrained by time and available resources, the sample size of this clinical cohort is relatively modest, and participants were recruited from a single institution, which may significantly restrict the generalizability of the present results. Future studies will combine co‑culture cell models with animal models to further elucidate the cell-type-specific functions of the miR-1290/TAOK1 axis, thereby enabling a more comprehensive evaluation of its regulatory role in sepsis. Meanwhile, large‑scale, multicenter prospective studies are warranted to further validate the clinical value of miR‑1290.

Conclusion

miR-1290 was downregulated in patients with sepsis and exhibited considerable value for disease diagnosis and prognostic evaluation. Functionally and mechanistically, miR-1290 negatively regulated LPS-induced reduction in macrophage viability, pro-inflammatory activation, and M1/M2 polarization imbalance via targeted inhibition of TAOK1, thereby exerting anti-inflammatory and protective effects in sepsis. Collectively, this study not only offers a novel candidate biomarker for the diagnosis and prognostic assessment of sepsis, but also offers a promising candidate target for targeted therapeutic intervention of this disease.

Supplementary Information

Below is the link to the electronic supplementary material.

Authors' contributions

Conceptualization, D.G., M.W.; Data curation, D.G., M.W.; Formal analysis, D.G., M.W.; Investigation, D.G.; Methodology, M.W.; Project administration, M.W.; Resources, D.G., M.W.; Software, D.G.; Supervision, M.W.; Validation, D.G., M.W.; Visualization, D.G., M.W.; Writing - original draft, D.G.; Writing - review & editing, M.W.

Funding

No funding was received to assist with the preparation of this manuscript.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The Ethics Committee of Renmin Hospital of Wuhan University approved this study. All methods were performed in accordance with relevant guidelines, regulations and the Declaration of Helsinki. Written informed consent was collected from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.