Objective <p>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.</p> Methods <p>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.</p> Results <p>TRG-AS1 is upregulated in CHF (<i>P</i> &lt; 0.0001) and is positively correlated with BNP (<i>r</i> = 0.500, <i>P</i> &lt; 0.0001) and CRP levels (<i>r</i> = 0.398, <i>P</i> &lt; 0.0001), while negatively correlated with LVEF (<i>r</i>=-0.605, <i>P</i> &lt; 0.0001). TRG-AS1 is an risk factor for poor patient prognosis (HR = 3.043, 95%CI: 1.359–6.816, <i>P</i> = 0.007) and possesses good diagnostic value (AUC = 0.895, 95%CI: 0.852–0.938, Sensitivity: 84.5%, Specificity: 80.0%, <i>P</i> &lt; 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 (<i>P</i> &lt; 0.01).</p> Conclusion <p>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.</p>

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

  • Ying Shi,
  • Wenhua Wang,
  • Chuanqing Weng,
  • Xiangyang Zhang

摘要

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.