Construction and analysis of the lncRNA‑miRNA‑mRNA network based on competitive endogenous RNA reveals functional genes in heart failure

Abstract

Heart failure (HF) is a principal cause of morbidity and mortality worldwide, affecting an estimated 38 million people. Although significant progress has been made with respect to the underlying molecular mechanisms, the role of the competing endogenous RNA (ceRNA) network in the pathogenesis of HF remains largely unknown. In this study, an HF-associated ceRNA network was constructed based on the differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs obtained, respectively, from the GSE77399, GSE104150 and GSE84796 datasets. The ceRNA network consisted of 12 lncRNA nodes, 43 miRNA nodes, 343 mRNA nodes and 530 edges. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the ceRNA network was primarily enriched in the immune response, inflammatory response and T cell and B cell receptor signaling pathways. In addition, three lncRNAs (growth arrest specific 5, taurine upregulated 1 and HOX transcript antisense RNA) and three miRNAs [hsa-miRNA (miR)-26b-5p, hsa-miR-8485 and hsa-miR-940] with higher node degrees compared with other genes were selected as hub nodes. The expression of hub nodes in patients with HF was verified by reverse transcription-quantitative polymerase chain reaction analysis. The present study provided further insights into the important roles of the ceRNA network in HF development, and indicated the potential use of these hub nodes as diagnostic biomarkers and therapeutic targets.

LncRNA TUG1 competitively binds to miR‐340 to accelerate myocardial ischemia‐reperfusion injury

“…Moreover, the previously conducted study by Su et al also revealed highly expressed TUG1 in H 2 O 2 ‐induced cardiomyocytes, which resulted in accelerated cell apoptosis and oxidative stress 25 . In contrast, it has also been previously reported that heart failure causes a significant downregulation of TUG1 in human blood 26 . In the current study, TUG1 expression was measured in cardiomyocytes of MIRI mouse models and H/R‐induced cardiomyocyte models.…”

“…25 In contrast, it has also been previously reported that heart failure causes a significant downregulation of TUG1 in human blood. 26 In the current study, TUG1 expression was measured in cardiomyocytes of MIRI mouse models and H/R-induced cardiomyocyte models. These may be the reason of different expressions of TUG1 detected.…”

ASPN is a Potential Promising Biomarker for Common Heart Failure

“…HF is the nal stage of various heart diseases, especially ICM and DCM, with high mortality and morbidity worldwide [25,26]. Although numerous studies have suggested the possible mechanisms of HF, they remain largely unknown and need further investigation.…”

Pseudogenes in Cardiovascular Disease

“…In this regard, tremendous effects have been made toward the elucidation of molecular mechanisms underlying various CVDs (Uchida and Dimmeler, 2015 ; Li S. et al, 2018 ). For example, expression of long non-coding RNAs (lncRNAs) has been detected under normal physiological conditions and in disease states, some lncRNAs are found to regulate acute myocardial infarction (such as Novlnc6) (Uchida and Dimmeler, 2015 ) and acute heart failure [such as Mhrt (Zhang et al, 2019 ), H19 (Greco et al, 2016 ), and growth arrest specific 5 (Wang G. et al, 2019 )], and gene transcripts such as MALAT1 and Tie-1-AS are found to control the growth and functions of blood vessels (Uchida and Dimmeler, 2015 ). Recently, Spinraza (a novel antisense oligonucleotide therapy) is approved by FDA to treat spinal muscular atrophy resulted from pseudogene SMN2, in which the antisense oligonucleotide is used to increase SMN2 exon 7 inclusion, thus increasing levels of survival motor neuron (SMN) protein (Chiriboga, 2017 ; Paton, 2017 ; Berciano et al, 2020 ).…”