| [1] PubMed ID: | 36826574 |
| Disease Name: | Heart Defects, Congenital |
| Tissue: | Blood |
| Dysfunction Pattern: | N/A |
| Validated Method: | RT-qPCR//High-throughput sequencing |
| Description: | As the most common congenital defective disorder in newborns, the pathogenesis of CHD is not yet clear [46]. With the continuous improvement of medical conditions and prenatal diagnostic techniques, the vast majority of CHDs can be detected during pregnancy, but it cannot be excluded that there are still some CHDs that cannot be detected throughout pregnancy. In the clinic, some simple types of CHD, such as atrial septal defects, patent ductus arteriosus, and ventricular septal defects, can be treated surgically after birth and have a good prognosis [47]. However, if there is no early detection and treatment of some complex types of CHD, such as hypoplastic left heart syndrome, even after multiple surgeries, the prognosis is poor [48]. Therefore, if we had a serum biomarker for more comprehensive screening and diagnosis of CHD from a different perspective based on routine cardiac ultrasonography, this would largely reduce the prevalence and mortality of CHD. Although many efforts have been made to identify biomarkers for CHD, there are currently no clear biomarkers in the clinic.
With the development of sequencing technology, a new class of ncRNA-tRFs has entered the scene of diagnostic and prognostic biomarkers. tRFs/tiRNAs are an important class of regulatory molecules that play an integral role in cellular functions, such as proliferation, differentiation, apoptosis, and biological processes, such as RNA modification, DNA damage repair, and regulation of gene expression, as well as in the development of many diseases [17,20,49,50,51]. tRFs/tiRNAs are also involved in pathological processes such as viral infection, tumorigenesis, and neurodegeneration. Given that tRFs/tiRNAs are widespread in nature and their expression is closely related to functions such as cell proliferation, tRFs/tiRNAs may be useful biomarkers in some cases. Therefore, we examined the expression of tRFs/tiRNAs in the serum of pregnant women and performed a biological analysis to verify whether tRFs/tiRNAs in the serum of pregnant women could be used as potential biomarkers for CHD. |
| Comparision: | Disease VS Control |
| Mechanism: | In this study, we first performed high-throughput sequencing of peripheral serum from pregnant women with fetal heart defects and normal fetal hearts. Based on the sequencing results, we selected the top 18 abnormally expressed tRFs/tiRNAs for qRT-PCR to verify the authenticity of the data. Then, the most up- or down-regulated and statistically significant tRFs/tiRNAs in serum samples from two groups of pregnant women were tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2, respectively. The qRT-PCR results showed that tRF-58:74-Gly-GCC-1 was significantly up-regulated in the disease group and tiRNA-1:35-Leu-CAG-1-M2 was down-regulated in the disease group compared to the control group, which was consistent with the sequencing results. Moreover, we unexpectedly found that tRF-58:74-Gly-GCC-1 was specifically expressed in the VSD group. However, abnormal tRFs/tiRNAs expression was not found in other types of CHD in clinical samples. Therefore, we conclude that tRF-58:74-Gly-GCC-1 plays a crucial role in the occurrence and development of ventricular septal defect. The possible reason for our failure to find differentially expressed in tRFs/tiRNAs other types of CHD is the small number of clinical samples. To further understand the underlying mechanism of tRFs/tiRNAs in the development of CHD, we performed GO and KEGG pathway analysis. The results showed that tRF-58:74-Gly-GCC-1 was enriched for target genes in biological processes and adrenergic signaling in cardiomyocytes signaling pathways in cardiomyocytes. Currently, a large body of evidence suggests that CHD occurs as a result of the accumulation of environmental risk factors and an individual’s factors, and that exobiotic metabolic processes such as the elimination of environmental teratogens play an important role in the development and progression of CHD [48,52,53]. Therefore, tRF-58:74-Gly-GCC-1 may be involved in the biological processes leading to the development of CHD. For tiRNA-1:35-Leu-CAG-1-M2, we found that its target genes were mainly enriched in positive regulation of catabolic and positive regulation of cellular catabolic processes, and therefore, tiRNA-1:35-Leu-CAG-1-M2 plays an important role in normal cell growth and development. Since these differential tRFs/tiRNAs biological processes are closely related to the development of CHD, it is particularly important to further explore the relevant molecular mechanisms. Finally, we constructed a PPI network with all target genes predicted by biological analysis in order to further explain the potential mechanisms of tRFs/tiRNAs involvement in CHD development. The results showed that H2AFX and HLTF were the central proteins of tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2, respectively. H2AFX plays an important role in DNA damage repair and DNA fragmentation during apoptosis. HLTF also promotes DNA damage repair. Therefore, we conclude that tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 could play a crucial role in DNA damage repair and cell growth and development. In conclusion, our findings suggest that tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 in the peripheral serum of pregnant women are most likely to serve as promising biomarker candidates. |
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