LncRNA TUG1 alleviates cardiac hypertrophy by targeting miR‐34a/DKK1/Wnt‐β‐catenin signalling

Abstract

Cardiac hypertrophy, classified as physiological and pathological hypertrophy, is an adaptive response of the heart to keep normal cardiac function in the condition of pathological injury or abnormal stress. 1 Physiological cardiac hypertrophy, caused by pregnancy or sports training, has normal morphological characteristics and helpful influences on the heart. 2 Pathological cardiac hypertrophy, accompanied by maladaptive cardiac remodelling, altered cardiac morphology as well as abnormal cardiac gene expressions, is the key induction factor for heart failure progression. 3 Although many factors have been confirmed to induce cardiac hypertrophy, 4 the underlying molecular mechanisms have not been stated clearly. LncRNAs, a series of highly conserved non-coding RNAs, are composed of more than 200 nucleotides. 5,6 With continuous advances in sequencing technology and large-scale genome sequencing projects, Abstract The current study was designed to explore the role and underlying mechanism of lncRNA taurine up-regulated gene 1 (TUG1) in cardiac hypertrophy. Mice were treated by transverse aortic constriction (TAC) surgery to induce cardiac hypertrophy, and cardiomyocytes were treated by phenylephrine (PE) to induce hypertrophic phenotype. Haematoxylin-eosin (HE), wheat germ agglutinin (WGA) and immunofluorescence (IF) were used to examine morphological alterations. Real-time PCR, Western blots and IF staining were used to detect the expression of RNAs and proteins. Luciferase assay and RNA pull-down assay were used to verify the interaction. It is revealed that TUG1 was up-regulated in the hearts of mice treated by TAC surgery and in PE-induced cardiomyocytes. Functionally, overexpression of TUG1 alleviated cardiac hypertrophy both in vivo and in vitro. Mechanically, TUG1 sponged and sequestered miR-34a to increase the Dickkopf 1 (DKK1) level, which eventually inhibited the activation of Wnt/β-catenin signalling.In conclusion, the current study reported the protective role and regulatory mechanism of TUG1 in cardiac hypertrophy and suggested that TUG1 may serve as a novel molecular target for treating cardiac hypertrophy. K E Y W O R D Scardiac hypertrophy, DKK 1, lncRNA TUG1, miR-34a, Wnt/β-catenin signalling

CBX2 depletion inhibits the proliferation, invasion and migration of gastric cancer cells by inactivating the YAP/β-catenin pathway

“…The results demonstrated that CBX2 knockdown elevated P-YAP levels and inhibited YAP expression in the cytoplasm and nucleus, suggesting that CBX2 knockdown promoted YAP translocation, causing the degradation of cytoplasmic YAP. In addition, YAP inhibition suppressed the expression of β-catenin and its downstream signaling molecules, including c-myc and cyclin D1 ( 24 ), which is consistent with the results of the present study. The current study revealed that YAP overexpression reversed the inhibitory effect of CBX2 knockdown on the β-catenin pathway.…”

“…To confirm whether the β-catenin signaling pathway is involved in the role of CBX2 in GC, shRNA-DKK1 was synthesized. As DKK1 is a negative regulator of Wnt/β-catenin signaling ( 24 ), DKK1 was silenced to activate β-catenin signaling. Due to its higher transfection efficiency, shRNA-DKK1-1 was selected for further use, as determined by RT-qPCR ( Fig.…”

Overexpression of lncRNA TUG1 Alleviates NLRP3 Inflammasome-Mediated Cardiomyocyte Pyroptosis Through Targeting the miR-186-5p/XIAP Axis in Coronary Microembolization-Induced Myocardial Damage

“…The lncRNA taurine-up regulated gene 1 (TUG1) was observed during genomic screening in taurine-exposed retinal cells that are much conserved in mammals ( 17 ). Current studies reveal the dynamic expression of TUG1 in the progression and diseases of the heart ( 18 , 19 ). It is, however, not known whether TUG1 may also regulate CME-induced myocardial damage and, if so, what mechanisms are involved.…”

The Complexity of FGF23 Effects on Cardiomyocytes in Normal and Uremic Milieu

“…DKK1 forms a tertiary complex with LRP5/6 and the cell surface co-receptor Kremen-1 with the subsequent internalization of the receptor complex, whereas sclerostin binds to LRP5/6 and prevents binding of Wnt ligands to Frizzled-LRP5/6 receptor complex [81]. Experimental studies indicate that increased DKK1 levels are associated with the alleviation of cardiac hypertrophy [82]. Targeting other parts of Wnt signaling, e.g., Disheveled depletion showed to attenuate left ventricular remodeling [74].…”