Knockdown of lncRNA TTTY15 alleviates myocardial ischemia–reperfusion injury through the miR‐374a‐5p/FOXO1 axis

Abstract

Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR‐374a‐5p against myocardial I/R injury. In this study, we explored the role of lncRNA TTTY15 and its potential interaction mechanisms with miR‐374a‐5p in myocardial I/R injury. The expression of TTTY15 was increased both in vitro and in vivo after myocardial I/R injury models according to quantitative real‐time polymerase chain reaction. Various assays were conducted to evaluate the regulatory relationship among TTTY15, miR‐374a‐5p, FOXO1, and autophagy in H9c2 and HL‐1 cells. The results showed that TTTY15 suppresses autophagy and myocardial I/R injury by targeting miR‐374a‐5p. We found that TTTY15 regulates miR‐374a‐5p, thus affecting FOXO1 expression and autophagy in myocytes during I/R. Furthermore, in an in vivo mouse model of myocardial I/R injury, suppression of TTTY15 successfully alleviated myocardial I/R injury. Our results reveal a novel feedback mechanism in which TTTY15 regulates miRNA processing and a potential target in myocardial I/R injury. TTTY15 is a promising therapeutic target for treating myocardial I/R injury.

MiR-27a-3p suppresses cerebral ischemia-reperfusion injury by targeting FOXO1

“…In our study, FOXO1 was found to be targeted by miR-27a-3p. FOXO1 upregulation could inhibit the cell growth [ 11 ], while Grb2 can promote the cell proliferation [ 29 ]. Thus, the different function between FOXO1 and Grb2 might result in this discrepancy.…”

“…In addition, some reports have indicated that FOXO1 can regulate the progression of I/R injury. For instance, Chen YQ et al found that FOXO1 could alleviate the progression of myocardial ischemia-reperfusion injury [ 11 ]; Wang D et al indicated that FOXO1 downregulation could inhibit the progression of renal ischemia-reperfusion injury [ 12 ]. Meanwhile, FOXO1 is known to promote the development of CI/R [ 13 ].…”

Mechanisms by which silencing long-stranded noncoding RNA KCNQ1OT1 alleviates myocardial ischemia/reperfusion injury (MI/RI)-induced cardiac injury via miR-377-3p/HMOX1

“…The lncRNA‒miRNA-mRNA ceRNA network has been shown to have an integral role in I/R injury [ 18 – 20 ], and Yipeng Mo et al [ 21 ] reported that lncRNA cardiac hypertrophy-related factor (CHRF) exacerbates myocardial I/R injury by regulating the miR-182-5p/ATG7 pathway to enhance autophagy. YongQuan Chen et al [ 22 ] found that knocking out lncRNA TTTY15 alleviates MI/RI through the miR-374a-5p/FOXO1 axis. MiR-377-3p is closely related to the proliferation, apoptosis, migration, and inflammation of vascular smooth muscle cells (VSMCs) [ 23 ].…”

Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review

“…Despite being a frequent entity in current gastroenterology practice, the physiopathology of IBS is not fully understood. It is considered to be a complex multifactorial disorder affected by several factors such as age, sex, genetics, diet, psychosocial status, altered microbiota, subclinical inflammation, and hypersensitivity of the neural network[ 7 , 8 ]. In recent years, accumulating evidence has suggested that the alteration of the gut microbiota plays an important role in the pathophysiology of IBS, as gut microbes exert effects on the host immune system, on gut barrier function, and on the brain-gut axis[ 9 , 10 ].…”