TRG-AS1 is upregulated in chronic heart failure, serves as a diagnostic and prognostic biomarker, and promotes oxidative stress and inflammation by sponging miR-139-5p, which in turn regulates downstream target RUNX1.
TRG-AS1 expression is significantly upregulated in chronic heart failure patients compared to controls.
TRG-AS1 positively correlates with BNP and CRP levels, and negatively correlates with left ventricular ejection fraction (LVEF) in CHF patients.
TRG-AS1 demonstrates good diagnostic value for distinguishing CHF patients from controls.
High TRG-AS1 expression is an independent risk factor for poor prognosis in CHF patients.
Knockout of TRG-AS1 enhances cardiomyocyte proliferation, reduces apoptosis, alleviates oxidative stress, and inhibits inflammatory factor release.
TRG-AS1 functions as a competing endogenous RNA (ceRNA) by sponging miR-139-5p, with RUNX1 identified as a downstream target gene of this axis.
This research suggests that a molecule called TRG-AS1—a type of long non-coding RNA (lncRNA) found in blood—is significantly elevated in patients with chronic heart failure (CHF) compared to healthy individuals. The study, involving 116 CHF patients, found that higher TRG-AS1 levels were linked to worse markers of heart function (lower ejection fraction), higher levels of heart failure biomarkers (BNP), and greater inflammation (CRP). Patients with higher TRG-AS1 had roughly three times the risk of poor outcomes, and a blood test measuring TRG-AS1 could distinguish heart failure patients from non-patients with about 85% sensitivity and 80% specificity, suggesting it could be useful as a diagnostic biomarker. The study also investigated how TRG-AS1 causes harm at the cellular level. It works by 'sponging' or blocking a protective small RNA molecule called miR-139-5p. When miR-139-5p is blocked by TRG-AS1, a downstream gene called RUNX1 becomes more active, leading to increased oxidative stress (cellular damage from reactive molecules), increased inflammation, reduced cell growth, and increased cell death in heart muscle cells. When TRG-AS1 was experimentally removed in cell studies, these harmful effects were reversed. This research suggests that the TRG-AS1/miR-139-5p/RUNX1 pathway plays a role in the progression of chronic heart failure. TRG-AS1 may serve as both a diagnostic tool and a potential therapeutic target, meaning that drugs designed to block TRG-AS1 or restore miR-139-5p activity could potentially help treat heart failure. However, these findings are based on cell experiments and clinical measurements and would require further validation in larger studies and animal models before any clinical application.
Shi Y, Wang W, Weng C, Zhang X. (2026). The highly expressed lncRNA TRG-AS1 in serum specifically inhibits miR-139-5p, thereby promoting oxidative stress and inflammation in heart failure.. Journal of cardiothoracic surgery. https://doi.org/10.1186/s13019-026-04629-1