LncRNA TUG1 Regulates Proliferation of Cardiac Fibroblast via the miR-29b-3p/TGF-β1 Axis

Abstract

Background: Atrial fibrillation (AF) is a very common clinical arrhythmia, accompanied by the overproliferation of cardiac fibroblasts (CFs). This study aimed to investigate the role of the long non-coding RNA(lncRNA) taurine upregulated gene 1 (TUG1) in the proliferation of CFs and further investigated its underlying mechanism.Methods: One hundred four paroxysmal AF patients and 94 healthy controls were recruited. Human cardiac fibroblasts (HCFs) were applied to establish an AF cell model through treatment with angiotensin II (AngII). qRT-PCR was used for the measurement of gene levels. The cell proliferation was detected by cell counting kit-8 (CCK-8). Luciferase reporter assay was performed for target gene analysis.Results: Elevated levels of TUG1 and low expression of miR-29b-3p were detected in the serum of AF patients compared with the healthy controls. Pearson's correlation analysis exhibited an inverse relationship between TUG1 and miR-29b-3p expression in AF patients (r = −7.106, p < 0.001). Knockdown of TUG1 inhibited AngII-induced CF proliferation. Taurine upregulated gene 1 (TUG1) functions as a competing endogenous RNA (ceRNA) for miR-29b-3p, and downregulation of miR-29b-3p reversed the role of TUG1 in CF proliferation. TGF-β1 is a direct target gene of miR-29b-3p.Conclusions: Long non-coding RNA taurine upregulated gene 1 is a key regulator in the occurrence of AF. Slicing TUG1 inhibits CF proliferation by regulating the miR-29b-3p/TGF-β1 axis.

Pinpointing Functionally Relevant miRNAs in Classical Hodgkin Lymphoma Pathogenesis

“…miR-130a-3p and miR-143-3p target TGF-beta in HEK-293T cells and mesangial renal cells [ 92 , 93 ]. Both miRNAs are downregulated in cHL, implying that their decreased levels may contribute to the elevated expression of TGF-beta [ 94 , 95 ].…”

Predictive Value of Serum microRNA-29b-3p in Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation

“…In addition, the incidence of AF recurrence after RFCA was higher in patients with low miR-29b-3p expression than that in patients with high miR-29b-3p expression, and the cumulative incidence of recurrence after RFCA was higher in patients with low miR-29b-3p expression. Although many studies have shown down-regulation of miR-29b in AF, 18 , 20 there are little data on the association between miR-29b-3p and AF ablation outcomes. Circulating miR-21 is associated with ablation success in patients with persistent AF who underwent catheter ablation.…”

“… 17 Moreover, microRNA-29b-3p (miR-29b-3p) can reduce the degree of atrial fibrosis and the expression levels of fibrosis markers and exhibits weak expression in the serum of AF patients. 18 , 19 Besides, miR-29b-3p expression is reduced in AF patients, and lncRNA 19 drives cardiac fibroblast proliferation and collagen production by inhibiting the miR-29b-3p-VEGFA-TGF-β axis. 20 However, the clinical significance and values of serum miR-29b-3p expression in predicting AF recurrence after RFCA have not been reported so far.…”

Long Non-Coding RNAs in Cardiac and Pulmonary Fibroblasts and Fibrosis

“…In cardiac fibroblasts, TUG1 sequesters miR-29c to promote the activation of murine cardiac fibroblasts to myofibroblasts under hypoxic conditions in vitro [ 45 ]. Another study showed that TUG1 sequesters miR-29b-3p , which targets TGFB1 (transforming growth factor beta 1) to regulate the proliferation of human cardiac fibroblasts treated with angiotensin II in vitro [ 46 ]. Given that fibrosis is a general disease mechanism for chronic inflammation, more fibromiRs will be shown to be sequestered by lncRNAs in cardiac fibroblasts and fibrosis in the near future.…”

“…To complicate the matter further, individual lncRNAs have been reported to sponge several miRNAs, as in the case of the lncRNA GAS5 (growth arrest specific 5), for miR-21 , miR-26a/b-5p , and miR-5325p in cardiac fibroblasts and fibrosis [ 47 , 48 , 49 , 50 ]. Another example is TUG1 , which sequesters miR-29b-3p , miR-29c , miR-133b , and miR-590 [ 45 , 46 , 51 , 52 ]. As there are more miRNAs being identified to bind these two exemplified lncRNAs in other cell types (e.g., cardiomyocytes, endothelial cells), cellular statuses, and diseases [ 51 , 52 , 53 , 54 , 55 , 56 , 57 ], it is important to perform a comparative study of lncRNAs and several miRNAs being reported to be sequestered by the target lncRNAs by measuring the copy numbers of each RNA species.…”