Chimeric RNA transcripts are formed when exons from two genes fuse together, often due to chromosomal translocations, transcriptional errors or trans-splicing effect. While these chimeric RNAs produce functional proteins only in certain cases, they play a significant role in disease phenotyping and progression. ChiTaRS 5.0 (http://chitars.md.biu.ac.il/) is the latest and most comprehensive chimeric transcript repository, with 111 582 annotated entries from eight species, including 23 167 known human cancer breakpoints. The database includes unique information correlating chimeric breakpoints with 3D chromatin contact maps, generated from public datasets of chromosome conformation capture techniques (Hi–C). In this update, we have added curated information on druggable fusion targets matched with chimeric breakpoints, which are applicable to precision medicine in cancers. The introduction of a new section that lists chimeric RNAs in various cell-lines is another salient feature. Finally, using text-mining techniques, novel chimeras in Alzheimer's disease, schizophrenia, dyslexia and other diseases were collected in ChiTaRS. Thus, this improved version is an extensive catalogue of chimeras from multiple species. It extends our understanding of the evolution of chimeric transcripts in eukaryotes and contributes to the analysis of 3D genome conformational changes and the functional role of chimeras in the etiopathogenesis of cancers and other complex diseases.
Many human genes are transcribed from both strands and produce sense-antisense gene pairs. Sense-antisense (SAS) chimeric transcripts are produced upon the coalescing of exons/introns from both sense and antisense transcripts of the same gene. SAS chimera was first reported in prostate cancer cells. Subsequently, numerous SAS chimeras have been reported in the ChiTaRS-2.1 database. However, the landscape of their expression in human cells and functional aspects are still unknown. We found that longer palindromic sequences are a unique feature of SAS chimeras. Structural analysis indicates that a long hairpin-like structure formed by many consecutive Watson-Crick base pairs appears because of these long palindromic sequences, which possibly play a similar role as double-stranded RNA (dsRNA), interfering with gene expression. RNA–RNA interaction analysis suggested that SAS chimeras could significantly interact with their parental mRNAs, indicating their potential regulatory features. Here, 267 SAS chimeras were mapped in RNA-seq data from 16 healthy human tissues, revealing their expression in normal cells. Evolutionary analysis suggested the positive selection favoring sense-antisense fusions that significantly impacted the evolution of their function and structure. Overall, our study provides detailed insight into the expression landscape of SAS chimeras in human cells and identifies potential regulatory features.
Cardiovascular diseases (CVDs) are of multifactorial origin and can be attributed to several genetic and environmental components. CVDs are the leading cause of mortality worldwide and they primarily damage the heart and the vascular system. Non-coding RNA (ncRNA) refers to functional RNA molecules, which have been transcribed into DNA but do not further get translated into proteins. Recent transcriptomic studies have identified the presence of thousands of ncRNA molecules across species. In humans, less than 2% of the total genome represents the protein-coding genes. While the role of many ncRNAs is yet to be ascertained, some long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been associated with disease progression, serving as useful diagnostic and prognostic biomarkers. A plethora of data repositories specialized in ncRNAs have been developed over the years using publicly available high-throughput data from next-generation sequencing and other approaches, that cover various facets of ncRNA research like basic and functional annotation, expressional profile, structural and molecular changes, and interaction with other biomolecules. Here, we provide a compendium of the current ncRNA databases relevant to cardiovascular research.
Background. Immunoglobulin superfamily member 10 (IGSF10) is a member of the immunoglobulin superfamily that is expressed at high levels in both the gallbladder and ovary. Currently, the role and possible mechanism of IGSF10 in breast cancer remain unclear. Method. By applying real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC), the expression of IGSF10 in breast cancer cells and tissues was detected. We collected the clinical information from 700 patients with breast cancer in The Cancer Genome Atlas (TCGA), and analyzed the relationship between IGSF10 expression and the clinicopathological features and survival outcomes of these patients. The potential mechanisms and pathways associated with IGSF10 in breast cancer were explored by performing a gene set enrichment analysis (GSEA). Results. According to TCGA data, qRT-PCR and IHC experiments, levels of the IGSF10 mRNA and protein were significantly decreased in breast cancer tissues. IGSF10 expression was significantly correlated with age, tumor size, and tumor stage. Moreover, shorter overall survival (OS) and relapse-free survival (RFS) correlated with lower IGSF10 expression, according to the survival analysis. The multivariate analysis identified that IGSF10 as an independent prognostic factor for the OS (hazard ratio (HR)=1.793, 95% confidence interval (CI): 1.141-2.815, P=0.011) and RFS (HR=2.298, 95% CI: 1.317-4.010, P=0.003) of patients with breast cancer. Based on the GSEA, IGSF10 was involved in DNA repair, cell cycle, and glycolysis. IGSF10 was also associated with the PI3K/Akt/mTOR and mTORC1 signaling pathways. Conclusions. This study revealed a clear relationship between IGSF10 expression and the tumorigenesis of breast cancer for the first time. Therefore, further studies are needed to understand the mechanism of IGSF10 in breast cancer.
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