The highly expressed lncRNA TRG-AS1 in serum specifically inhibits miR-139-5p, thereby promoting oxidative stress and inflammation in heart failure.

Abstract

Objective: Patients with chronic heart failure (CHF) have a high mortality rate. The aim of this research is to examine the clinical value and molecular mechanisms of the lncRNA T cell receptor gamma chain-associated AS1 (TRG-AS1) in CHF.

Methods: The TRG-AS1 expression in 116 CHF patients was assessed by qRT-PCR. The diagnostic and prognostic value of TRG-AS1 was evaluated through ROC and COX survival analysis. The correlation between TRG-AS1 and clinical parameters was examined using Pearson's correlation analysis. Cell growth and death were assessed using the CCK-8 assay and double-staining methods. ELISA was used to detect inflammatory factors. The DLR assay was used to verify the interaction between TRG-AS1, miR-139-5p, and RUNX1.

Results: TRG-AS1 is upregulated in CHF (P < 0.0001) and is positively correlated with BNP (r = 0.500, P < 0.0001) and CRP levels (r = 0.398, P < 0.0001), while negatively correlated with LVEF (r=-0.605, P < 0.0001). TRG-AS1 is an risk factor for poor patient prognosis (HR = 3.043, 95%CI: 1.359-6.816, P = 0.007) and possesses good diagnostic value (AUC = 0.895, 95%CI: 0.852-0.938, Sensitivity: 84.5%, Specificity: 80.0%, P < 0.0001). Knocking out TRG-AS1 enhances cell proliferation, reduces apoptosis, alleviates oxidative stress, and inhibits the release of inflammatory factors by reducing the binding to miR-139-5p (P < 0.01).

Conclusion: TRG-AS1 may serve as a new diagnostic biomarker for CHF. The TRG-AS1/miR-139-5p axis may represent a potential therapeutic target for CHF. Furthermore, RUNX1 has been preliminarily identified as a downstream target gene of this ceRNA.