Alternative splicing plays a key role in posttranscriptional regulation of gene expression, allowing a single gene to encode multiple protein isoforms. As such, alternative splicing amplifies the coding capacity of the genome enormously, generates protein diversity, and alters protein function. More than 90% of human genes undergo alternative splicing, and alternative splicing is especially prevalent in the nervous and immune systems, tissues where cells need to react swiftly and adapt to changes in the environment through carefully regulated mechanisms of cell differentiation, migration, targeting, and activation. Given its prevalence and complexity, this highly regulated mode of gene expression is prone to be affected by disease. In the following review, we look at how alternative splicing of signaling molecules—cytokines and their receptors—changes in different pathological conditions, from chronic inflammation to neurologic disorders, providing means of functional interaction between the immune and neuroendocrine systems. Switches in alternative splicing patterns can be very dynamic and can produce signaling molecules with distinct or antagonistic functions and localization to different subcellular compartments. This newly discovered link expands our understanding of the biology of immune and neuroendocrine cells, and has the potential to open new windows of opportunity for treatment of neurodegenerative disorders.

Introduction: Recently, miRNAs have become popular molecules used as non-invasive biomarkers in cancer diseases. Aim: The aim of the study was to explore the expression of four miRNAs isoforms: miR-31-3p, miR-196a-5p, miR-210-3p and miR-424-5p in plasma and tissue samples from patients with advanced laryngeal squamous cell carcinoma (LSCC) and healthy controls. Materials and methods: Fresh-frozen tumour and normal laryngeal tissue as well as plasma samples were obtained from 22 patients diagnosed with advanced LSCC. The control group included plasma samples from 21 cancer-free volunteers. Total RNA (including miRNAs) extraction, reverse transcription and real time qPCR were the laboratory techniques used in the study. The obtained results were analyzed using SPSS software v. 23. Results: We found that miR-31-3p, miR-196a-5p, and miR-210-3p levels were significantly elevated in laryngeal tumour tissue, but only the levels of miR-31-3p and miR-196a-5p were significantly upregulated in the plasma LSCC target group. Positive correlation was obtained for miR-31-3p (rs=0.443, p=0.039) and miR-196a-5p (rs=0.548; p=0.008) between plasma and adjacent tumour tissue LSCC samples. ROC analyses were used to evaluate the discriminative power of both miRNAs alone and in combination. The combination of miR-31-3p and miR-196a-5p showed best results with AUC=0.978 (95% CI: 0.945&ndash;1.000, p<0.001) with 100% sensitivity and 81% specificity at cut-off: RQ=2.99. Conclusions: Based on this miR-31-3p and miR-196a-5p are proposed as potential biomarkers for validation in larger LSCC group and could be included in a non-invasive miRNAs set for detection of advanced LSCC.

The ever-growing number of methods for the generation of synthetic bulk and single cell RNA-seq data have multiple and diverse applications. They are often aimed at benchmarking bioinformatics algorithms for purposes such as sample classification, differential expression analysis, correlation and network studies and the optimization of data integration and normalization techniques. Here, we propose a general framework to compare synthetically generated RNA-seq data and select a data-generating tool that is suitable for a set of specific study goals. As there are multiple methods for synthetic RNA-seq data generation, researchers can use the proposed framework to make an informed choice of an RNA-seq data simulation algorithm and software that are best suited for their specific scientific questions of interest.

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