Expression profiles and functional analysis of tRNA-derived small RNAs in epicardial adipose tissue of patients with heart failure

Abstract

Background

Heart failure is considered an epidemic disease in the modern world. Since it presents as a multifactorial, systemic disease, a comprehensive understanding of the underlying mechanism is essential. Epicardial adipose tissue (EAT) is increasingly recognized to be metabolically active and is able to secrete myriad bioactive molecules, including exosomes carrying tRNA-derived small RNAs (tsRNAs). Mounting evidence has suggested that these specific tsRNAs dynamically impact fundamental cellular processes, but no studies have focused on the influence of tsRNA in EAT on cardiac dysfunction.

Methods

To investigate the regulatory mechanism of tsRNAs of EAT associated with HF, we collected EAT from HF (n = 5) patients and controls (n = 5) and used a combination of RNA sequencing, quantitative reverse transcription-polymerase chain reaction (qRT–PCR) and bioinformatics to screen the expression profiles of tsRNAs in HF.

Results

We ultimately identified an expression profile of 343 tsRNAs in EAT. Of those, a total of 24 tsRNAs were significantly differentially expressed between HF and controls: 17 were upregulated and 7 were downregulated (fold change >1.5, p < 0.05). Four tsRNAs (tiRNA-Pro-TGG-001, tRF-Met-CAT-002, tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011) were randomly selected and validated by qRT–PCR. Bioinformatics analyses revealed a dense interaction of target genes between tRF-Tyr-GTA-010 and tRF-Tyr-GTA-011. Based on functional analysis, these two tRFs might play a protective role by regulating sphingolipid and adrenergic signaling pathways by targeting genes mainly contributing to calcium ion transport.

Conclusions

Our study profiled tsRNA expression in EAT with HF and identified a comprehensive dimension of potential target genes and tsRNA-mRNA interactions.

KEY MESSAGES

1. The development of heart failure involves a complex mechanistic network, which until now, has not been clarified.

2. Excess epicardial adipose tissue may promote heart failure via unknown mechanisms.

3. Our current study profiled transfer RNAs expression in epicardial adipose tissue with heart failure and identified a comprehensive dimension of potential target genes and transfer RNAs -mRNA interactions for the pathogenesis of deterioration in cardiac function.

Keywords:

• Heart failure
• epicardial adipose tissue
• tsRNAs
• sequencing
• bioinformatics

Authors’ contributions

LZ and PXS designed the study. LZ acquired the data. YSP did the analysis and interpretation of data. LZ wrote the manuscript and revised the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are openly available in Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE210707, reference number (GSE210707).

Additional information

Funding

No funding was received.