Project description:Background: Congenital heart disease (CHD) is one of the most predominant birth defects that cause 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 abnormal fetal heart and 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, 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.
Project description:Breast cancer is one of the most common cancers in the world and non-triple-negative breast cancer (non-TNBC) accounts for 80-90% of all invasive breast cancers. Early detection of breast cancer is considered as key to successful treatment. Conventionally,breast imaging and needle core biopsy are used for detection and monitoring of disease progression. However, small volume changes may be ignored on imaging and traditional biopsy is spatially and temporally limited, leading to a significant lag time in detecting cancer progression. This thus prompted renewed focus on early and accurate diagnosis. In this article, we committed to investigate whether there exists accurate molecule in peripheral blood which can help diagnose breast cancer. tRNA-derived fragments (tRFs) have been reported to be involved in many pathological processes, but whether it can serve as biomarkers for the diagnosis of breast cancer remains unclear. Using high-throughput sequencing technology, we identified 4021 differentially expressed tRFs in normal breast epithelial cell lines and non-triple-negative breast cancer cell lines and 8 tRFs were selected to construct a signature to predict the non-TNBC. Further, qRT-PCR was conducted to verify its expression and to analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR-7816, tDR-5334, tDR-4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR-7816 influences xenobiotic metabolic process that support the oncogenesis of breast cancer. Taken together, our results provide a rationale for using circulating tDR-7816 expression as a novel potential biomarker to diagnose early non-TNBC patients.
Project description:To explore the potential involvement of tRNA derived fragments (tRFs) in the human aortic vascular smooth muscle cells (HASMCs), we conducted tRFs profiling in three pairs of differentiated HASMCs (treated with PBS) and dedifferentiated HASMCs (treated with PDGF-BB 50 ng/ml) by microarray. Our results showed that tRFs were aberrantly expressed in dedifferentiated HASMCs compared with differentiated HASMCs and provided potential targets for novel insights into VSMC differentiation or vascular remodeling diseases.
Project description:The development of non-invasive diagnostic methods is crucial in early disease detection and thus better treatment options. Small RNAs have been identified as good candidates for such diagnostic markers due to their small size, which allows ease of transport from live cells. Correlating small RNAs in bodily fluid with those in tissue cells of interest may even shed light on disease mechanisms and the development of therapeutic targets. tRNA-derived RNA fragments (tRFs), a family of recently discovered small non-coding RNAs (sncRNAs), have been found to be significantly changed in various disease states, including Alzheimer's disease (AD), the most common type of dementia. Previously, tRFs have been found to be significantly enhanced in human AD hippocampus tissues. However, whether tRFs change in body fluids is unknown. In this study, we planned to identify baselines for potential usage of tRFs as biomarkers in cerebrospinal fluid and blood serum for future development of AD biomarkers. Towards this goal, we used T4 polynucleotide kinase-RNA-seq, a modified next-generation sequencing technique, to identify detectable tRFs in human cerebrospinal fluid (CSF) and serum samples. Interestingly, we found an abundance of tRFs in both CSF and serum samples in comparison to microRNAs, well-known small RNAs (about 3-10 times higher in read counts). This clearly indicates the significant potential of tRFs as non-invasive biomarkers in CSF and serum.
Project description:tRNA related fragments(tRF) and tRNA halves(tiRNA) are novel class of short non-coding RNA derived from tRNAs. Using RNA sequencing, we evaluated the tRFs/tiRNAs expression profiles in relapsed/refractory multiple myeloma and multiple myeloma patients. Bioinformatics analyses indicated that tRFs/tiRNAs may be involved in the progression and drug-resistance of multiple myeloma.
Project description:tRNA-derived small RNA including tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) plays significant roles in the various molecular mechanisms that underlie certain human diseases. of the generation of tRFs/tiRNAs and their potential roles during Dengue virus (DENV) infection is not yet known. Here, we have performed small RNA sequencing to identify the generation and alterations in tRF expression profiles of DENV infected Huh7 cells. Our results suggest that 733 tiRNAs/tRFs were found to be differentially expressed during DENV infection. Interestingly, 3’tRF population were found to be upregulated and i-tRF population were found to be downregulated. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze the impact of differentially expressed tRFs on DENV pathogenesis. Our results suggest the significant involvement in transcriptional regulation via RNA polymerase II promoter and metabolic pathways. Overall, our study contributes significantly to our understanding of the roles played by tRFs in the complex dynamics of DENV infection.