Acute heart failure caused by progressive heart failure is a common disease in ICU. These patients often require mechanical ventilation and renal replacement therapy, which results in an increased economic burden for patients and their families[18]. Therefore, it is important to identify the molecular mechanism by which heart failure occurs and to identify treatment for this mechanism. Recently, the mechanism of ceRNA has attracted increasing attention. The relationship among lncRNA, miRNA and mRNA play an important role in the regulation of multiple processes. At present, numerous studies have been conducted on the ceRNA molecular mechanism of heart failure. Zhang et al have found that lncRNA-CHAR/miR-20b/PTEN play an important role in the progression of cardiac hypertrophy[19]. The research of Liang et al showed that lncRNA PFL contributes to cardiac fibrosis by acting miRNA-let-7d[20].
In the present study, we analyzed the datasets of GSE9128, GSE61741 and GSE77399 to find more possible molecular mechanism of ceRNA in heart failure. Based on the ceRNA theory and above series of analyses, network of ceRNA which include 7 mRNAs (BCL2A1, DUSP1, EGR1, MYC, NR4A2, PTGS2 and RAC2), 3 miRNAs (miR-20a, miR-129-59 and miR-185-5p) and 3 lncRNAs (GAS5, H19 and PCGEM1) were obtained. MYC played critical roles in heart failure development progress[21]. NR4A2 is a member of the NR4A orphan nucleus receptor family. NR4A2 has protective function for cardiomyocytes against myocardial infarction[22]. DUSP1 can regulate cardiac metabolism. Overexpress DUSP1 can alleviate the fatal mitochondrial fission and provide a survival advantage to myocardial tissue[23]. The level of EGR1 is related to effectiveness of percutaneous coronary intervention. If the level of EGR1 is significant decreased in the early postoperative period, the patient may be suspected of having no-reflow[24]. PTGS2 (cyclooxyfenase-2) represents a key enzyme in arachidonic acid metabolism in health and disease. It is expressed in several human tissues and induced in various cell types in response to inflammatory cytokine[25]. BCL2A1 and RAC2 have not been reported in the progression of heart failure. BCL2A1 is one of B-cell lymphoma2 (BCL2) proteins which are important cell death regulators. BCL2A1 is overexpressed in a variety of cancer cells, including hematological malignancies and solid tumors, and may contribute to tumor progression[26]. RAC2 is a GTpase that is exclusively expressed in hematopoietic cells. Mutations in RAC2 is associated with immunodeficiencies in some patients[27].
In previous study, the expression of miR-20a-5p is associated with the degree of left ventricular dilation[28]. Downregulation of miR-129-5p was observed in the serum of chronic heart failure patients. miR-129-5p mimic improved heart function and hemodynamic parameters[29]. At present, the study of miR-185-5p associated with heart failure is rare. There are some researches about miR-185-5p in the field of cancer. miR-185-5p was proved that it can inhibit cell metastasis of HCC by suppressing ROCK2[30]. Zhang et al found that expression of plasma H19 was high and it was independent predictors for coronary artery disease[31]. Li et al have found that the expression of GAS5 was low in peripheral blood of chronic heart failure[32]. These researches and findings are consistent with our results. At present, the study of PCGEM1 in heart failure was rare. There were some researches of PCGEM1 about cancers. In the research of Ho et al, they found that PCGEM1 is often upregulated in prostate cancer[33]. PCGEM1 also promotes cell proliferation, migration and invasion in cervical cancer[34]. Therefore, further study about the function and expression of PCGEM1 in heart failure is needed to identify. These findings indicate that these lncRNAs and miRNAs may have profound function in the progression of heart failure. Therefore, further studies about these mRNAs, lncRNAs and miRNAs are needed to identify their relationship and mechanisms.
There are several limitations in the present study. Firstly, we only have a result of bioinformatics analysis. Therefore, future in vitro and in vivo experiments are required to verify these results in heart failure pathology. Secondly, studies with larger cohorts of patients with heart failure are required to confirm the diagnostic and therapeutic value of the identified ceRNAs.
In conclusion, in the present study, we have performed a bioinformatics analysis to identify ceRNA network that may be involved in the progression of heart failure. In the present study, based on the ceRNA theory and above series of analyses, network of ceRNA which include 7 mRNAs (BCL2A1, DUSP1, EGR1, MYC, NR4A2, PTGS2 and RAC2), 3 miRNAs (miR-20a, miR-129-59 and miR-185-5p) and 3 lncRNAs (GAS5, H19 and PCGEM1) were obtained. These findings can be used to carrying on further study to identify the biological function, appropriate treatment targets and biomarkers in the progression of heart failure.