miR-454-3p alleviates LPS-induced cardiomyocyte damage by negatively regulating STAT3 in sepsis-induced cardiomyopathy.

Authors

Zimo Sha, Tianzhichao Hou, Taojie Zhou, Yangyang Bao, Yue Wei, Tianyou Ling, Liqun Wu

Published in

Internal and emergency medicine. Oct 03, 2026. Epub Oct 03, 2026.

Abstract

Sepsis-induced cardiomyopathy (SICM) contributes greatly to high mortality in critically ill patients. Accumulating evidence indicates that miRNAs play key roles in sepsis-related organ injury. This work investigated the function and molecular mechanism of miR-454-3p in SICM, along with its potential clinical utility. A total of 100 healthy controls and 210 sepsis patients were enrolled. Sepsis patients were categorized into non-cardiomyopathy group (non-CM, n=105) and SICM group (n=105). Receiver operating characteristic (ROC) curve analysis, multivariate logistic regression, and Cox regression were performed to assess the clinical value of miR-454-3p. In vitro functional experiments were conducted using LPS-stimulated AC16 cardiomyocytes. The dual-luciferase reporter assay verified the targeting relationship between miR-454-3p and STAT3. miR-454-3p expression decreased progressively from healthy controls to non-CM patients and further to SICM patients. miR-454-3p demonstrated good diagnostic performance for SICM. Multivariate analysis identified miR-454-3p as both an independent protective factor against SICM and an independent predictor of favorable prognosis. Cellular experiments revealed that miR-454-3p directly binds to the 3'UTR of STAT3 and suppresses STAT3 expression. Functional assays indicated that miR-454-3p attenuates LPS-induced cardiomyocyte apoptosis, inflammation, and oxidative stress, whereas STAT3 overexpression reverses these protective phenotypes. Furthermore, western blot analysis showed that miR-454-3p inhibits activation of the JAK2/STAT3/NF-κB inflammatory cascade. In vitro assays suggest that miR-454-3p alleviates LPS-triggered cardiomyocyte damage by negatively regulating STAT3 and suppressing the JAK2/STAT3/NF-κB inflammatory cascade. Our single-center observational data indicate that circulating miR-454-3p correlates independently with SICM incidence and 28-day all-cause mortality, implying its potential value as a candidate diagnostic and prognostic biomarker for SICM. Nevertheless, correlational findings from this cross-sectional cohort cannot confirm causal relationships, and large-scale multicenter prospective cohorts are needed for external validation to verify its clinical utility.

PMID:
42829404
Bibliographic data and abstract were imported from PubMed on 04 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.