Maternal Serum tRNA-Derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease

Abstract

Background: Congenital heart disease (CHD) is one of the most predominant birth defects that causes infant death worldwide. The timely and successful surgical treatment of CHD on newborns after delivery requires accurate detection and reliable diagnosis during pregnancy. However, there are no biomarkers that can serve as an early diagnostic factor for CHD patients. tRNA-derived fragments (tRFs) have been reported to play an important role in the occurrence and progression of numerous diseases, but their roles in CHD remains unknown. Methods: High-throughput sequencing was performed on the peripheral blood of pregnant women with an abnormal fetal heart and a normal fetal heart, and 728 differentially expressed tRFs/tiRNAs were identified, among which the top 18 tRFs/tiRNAs were selected as predictive biomarkers of CHD. Then, a quantitative reverse transcriptase polymerase chain reaction verified the expression of tRFs/tiRNAs in more clinical samples, and the correlation between tRFs/tiRNAs abnormalities and CHD was analyzed. Results: tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 may be promising biomarkers. Through further bioinformatics analysis, we predicted that TRF-58:744-GLy-GCC-1 could induce CHD by influencing biological metabolic processes. Conclusions: Our results provide a theoretical basis for the abnormally expressed tRF-58:74-Gly-GCC-1 in maternal peripheral blood as a new potential biomarker for the accurate diagnosis of CHD during pregnancy.

Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis

“…Statistical analysis was conducted using either Student’s t-test or one-way ANOVA, with a p-value<0.05 indicating statistical significance. To guarantee the dependability of the findings, the experiments were conducted a minimum of three times ( 27 , 28 ).…”

“…The volume of osteophytes or bone spurs was quantified to assess the extent of joint damage in knee osteoarthritis. Furthermore, each sample was given a macroscopic rating using a previously documented technique that quantitatively assesses the severity of OA (26).…”

Transcriptome studies of congenital heart diseases: identifying current gaps and therapeutic frontiers

“…tRNA was first thought to be stable, however, recent developments in unbiased high-throughput sequencing facilitated the discovery of a new class of tRNA: tRNA halves (31–40 nucleotides) and tRNA-derived fragments (tRFs, 14–30 nucleotides) ( Cole et al, 2009 ; Lee et al, 2009 ; Liao et al, 2010 ). While our current understanding of the functional role of transfer RNA fragment (tRF) in CHD is still in its infancy, the pioneering study of Lu et al, 2023 has shown that distinct tRNA fragments might serve as a biomarker for accurate diagnosis of CHD during pregnancy. Here, 18 tRFs/tiRNAs were selected as predictive biomarkers of CHDs.…”

“…Here, 18 tRFs/tiRNAs were selected as predictive biomarkers of CHDs. By further analysis, tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 were validated as promising biomarkers of CHD ( Lu et al, 2023 ). The onset and progress of CHD, mainly in early pregnancy, is a complex and relatively long-term process involving many genetic and epigenetic alterations.…”