Differentially expressed TUG1 and miR-145-5p indicate different severity of chronic heart failure and predict 2-year survival prognosis

Abstract

Long non-coding RNAs (lncRNAs) and microRNAs (miRs) have critical roles in the progression of various diseases. The present study aimed to investigate the levels and clinical significance of lncRNA taurine upregulated gene 1 (TUG1) and miR-145-5p in patients with chronic heart failure (CHF) and explore their indicative value regarding disease severity. TUG1 and miR-145-5p levels were detected by reverse-transcription quantitative PCR. Correlations were examined using Pearson's correlation analysis. Receiver operating characteristic analysis was used to evaluate the diagnostic value of TUG1, miR-145-5p and brain natriuretic peptide (BNP). Survival analysis was performed by the Kaplan-Meier method. Cox regression analysis was used to evaluate the prognostic value of TUG1 and miR-145-5p. The levels of interleukin-6 and tumor necrosis factor-α in serum were detected by ELISA. The results indicated that TUG1 was upregulated and miR-145-5p was downregulated in patients with CHF and they were negatively correlated. TUG1 and miR-145-5p were associated with the left ventricle ejection fraction and were able to indicate the severity of CHF. Serum TUG1 and miR-145-5p had a certain diagnostic value and the combination of BNP, TUG1 and miR-145-5p had high diagnostic accuracy. TUG1 and miR-145-5p were closely associated with overall survival and may function as independent prognostic biomarkers for patients with CHF. In addition, TUG1 and miR-145-5p levels were markedly correlated with inflammation in CHF. Upregulated TUG1 and downregulated miR-145-5p may indicate the severity of CHF, may serve as diagnostic and prognostic biomarkers and may be involved in CHF progression by regulating inflammatory responses.

Keywords: TUG1; chronic heart failure; diagnosis; inflammation; miR-145-5p; prognosis; severity.

Figure 1

Aberrant expression of TUG1 and miR-145-5p in patients with CHF. (A) Binding sites of TUG1 with miR-145-5p. (B) Relative TUG1 expression in patients with CHF and controls. (C) Relative miR-145-5p expression in patients with CHF and controls. (D) Negative correlation between TUG1 and miR-145-5p expression (r=-0.809, P<0.001). ^***P<0.001 vs. Controls. The values are expressed as the median (interquartile range) in the box plots. TUG1, taurine upregulated gene 1; miR, microRNA; CHF, chronic heart failure.

Figure 2

Correlation of the TUG1/miR-145-5p interaction with LVEF and severity of CHF in patients. (A) Negative correlation between relative TUG1 expression and LVEF (r=-0.554, P<0.001). (B) Positive correlation between relative miR-145-5p expression and LVEF (r=0.377, P<0.001). (C) Relative TUG1 expression in patients with CHF with NYHA class II, III and IV. (D) Relative miR-145-5p expression in patients with CHF with NYHA class II, III and IV. ^***P<0.001 vs. patients with NYHA class II; ^###P<0.001 vs. patients with NYHA class III. The values are expressed as the median (interquartile range) in the box plots. TUG1, taurine upregulated gene 1; miR, microRNA; LVEF, left ventricle ejection fraction; NYHA, New York Heart Association; CHF, chronic heart failure.

Figure 3

Diagnostic value of BNP and TUG1/miR-145-5p interaction for screening patients with CHF. BNP, brain natriuretic peptide; TUG1, taurine upregulated gene 1; miR, microRNA; AUC, area under the receiver operating characteristic curve; CHF, chronic heart failure.

Figure 4

Relationship between TUG1/miR-145-5p interaction and survival of patients with CHF. (A) Association between TUG1 expression and overall survival of patients with CHF (log-rank P=0.009). (B) Association between miR-145-5p expression and overall survival of patients with CHF (log-rank P=0.024). TUG1, taurine upregulated gene 1; miR, microRNA; CHF, chronic heart failure.

Figure 5

Correlation of TUG1/miR-145-5p interaction with the levels of CRP and pro-inflammatory cytokines in patients with CHF. (A-C) Positive correlation of TUG1 expression with (A) CRP (r=0.557, P<0.001), (B) IL-6 (r=0.300, P=0.003) and (C) TNF-α (r=0.486, P<0.001). (D-F) Negative correlation of miR-145-5p expression with (D) CRP (r=-0.526, P<0.001), (E) IL-6 (r=-0.267, P=0.008) and (F) TNF-α (r=-0.432, P<0.001). TUG1, taurine upregulated gene 1; miR, microRNA; CHF, chronic heart failure; CRP, C-reactive protein; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α.