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Circular RNAs (circRNAs) are single-stranded and covalently closed non-coding RNA molecules originated from RNA splicing. Their functions include regulatory potential over other RNA species, such as microRNAs, messenger RNAs and RNA binding proteins. For circRNA identification, several algorithms are available and can be classified in two major types: pseudo-reference-based and split-alignment-based approaches. In general, the data generated from circRNA transcriptome initiatives is deposited on public specific databases, which provide a large amount of information on different species and functional annotations. In this review, we describe the main computational resources for the identification and characterization of circRNAs, covering the algorithms and predictive tools to evaluate its potential role in a particular transcriptomics project, including the public repositories containing relevant data and information for circRNAs, recapitulating their characteristics, reliability and amount of data reported., (© The Author(s) 2023. Published by Oxford University Press.)

Tuberculosis (TB) is one of the most fatal infectious diseases, caused by the aerobic bacteria Mycobacterium tuberculosis . It is estimated that one-third of the world's population is infected with the latent (LTB) version of this disease, with only 5-10% of infected individuals developing its active (ATB) form. Pulmonary adenocarcinoma (PA) is the most common and diverse form of primary lung carcinoma. The simultaneous or sequential occurrence of TB and lung cancer in patients has been widely reported and is known to be an issue for diagnosis and surgical treatment. Raising evidence shows that patients cured of TB represent a group at risk for developing PA. In this work, using sRNA-sequencing, we evaluated the expression patterns of circulating small RNAs available in exosomes extracted from blood samples of Peruvian patients affected by latent tuberculosis, active tuberculosis, or pulmonary adenocarcinoma. Differential expression analysis revealed a set of 24 microRNAs perturbed in these diseases, revealing potential biomarker candidates for the Peruvian population. Most of these miRNAs are normally expressed in healthy lung tissue and are potential regulators of different shared and unique KEGG pathways related to cancers, infectious diseases, and immunology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guio, Aliaga-Tobar, Galarza, Pellon-Cardenas, Capristano, Gomez, Olivera, Sanchez and Maracaja-Coutinho.)

MicroRNAs (miRNAs) are small non-coding RNAs (sRNA), that alter gene expression by binding to target messenger RNAs (mRNAs) and repressing translation. Dysregulated miRNA expression has been implicated in the pathogenesis of autoimmune diseases such as Sjögren's syndrome (SS). The aim of this study was to characterize the global profile of sRNAs in labial salivary glands (LSG) from SS-patients and to validate potential miRNA candidates implicated in glandular inflammation. LSG from 21 SS-patients and 9 sicca controls were analyzed. A global next generation sequencing (NGS)-based sRNA profiling approach was employed to identify direct targets whereby differentially expressed miRNAs were predicted using bioinformatics tools. miRNA levels were validated by TaqMan and target mRNA levels were determined by quantitative real-time PCR. We also performed in vitro assays using recombinant TNF-α. NGS shows that ~30% of sRNAs were miRNAs. In comparison with samples from sicca controls, four miRNAs were found differentially expressed in LSG from SS-patients with low focus score (LFS) and 18 from SS-patients with high focus score (HFS). The miRNA with the most significant changes identified by NGS was hsa-miR-181d-5p and downregulation was confirmed by TaqMan analysis. Levels of TNF-α mRNA, a direct target of hsa-miR-181d-5p, were significantly increased and negatively correlated with hsa-miR-181d-5p presence. Moreover, positive correlations between TNF-α transcript levels, focus score, ESSDAI, and autoantibody levels were also detected. Furthermore, TNF-α stimulation decreased hsa-miR-181d-5p levels in vitro . Downregulation of hsa-miR-181d-5p in LSG from SS-patients could contribute to the glandular pro-inflammatory environment by deregulation of its direct target TNF-α. Further dissection of the pathophysiological mechanisms underlying the hsa-miR-181d-5p-mediated action in inflammatory conditions could be useful to evaluate the benefits of increasing hsa-miR-181d-5p levels for restoration of salivary gland epithelial cell architecture and function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castro, Carvajal, Jara, Aguilera, Heathcote, Barrera, Aliaga-Tobar, Maracaja-Coutinho, Urzúa, Quest, González, Molina, Hermoso and González.)

We explored sex-biased effects of the primary stress glucocorticoid hormone corticosterone on the miRNA expression profile in the rat hippocampus. Adult adrenalectomized (ADX) female and male rats received a single corticosterone (10 mg/kg) or vehicle injection, and after 6 h, hippocampi were collected for miRNA, mRNA, and Western blot analyses. miRNA profiling microarrays showed a basal sex-biased miRNA profile in ADX rat hippocampi. Additionally, acute corticosterone administration triggered a sex-biased differential expression of miRNAs derived from genes located in several chromosomes and clusters on the X and 6 chromosomes. Putative promoter analysis unveiled that most corticosterone-responsive miRNA genes contained motifs for either direct or indirect glucocorticoid actions in both sexes. The evaluation of transcription factors indicated that almost 50% of miRNA genes sensitive to corticosterone in both sexes was under glucocorticoid receptor regulation. Transcription factor-miRNA regulatory network analyses identified several transcription factors that regulate, activate, or repress miRNA expression. Validated target mRNA analysis of corticosterone-responsive miRNAs showed a more complex miRNA-mRNA interaction network in males compared to females. Enrichment analysis revealed that several hippocampal-relevant pathways were affected in both sexes, such as neurogenesis and neurotrophin signaling. The evaluation of selected miRNA targets from these pathways displayed a strong sex difference in the hippocampus of ADX-vehicle rats. Corticosterone treatment did not change the levels of the miRNA targets and their corresponding tested proteins. Our data indicate that corticosterone exerts a sex-biased effect on hippocampal miRNA expression, which may engage in sculpting the basal sex differences observed at higher levels of hippocampal functioning.

Angiotensin-(1-9) is a peptide from the noncanonical renin-angiotensin system with anti-hypertrophic effects in cardiomyocytes via an unknown mechanism. In the present study we aimed to elucidate it, basing us initially on previous work from our group and colleagues who proved a relationship between disturbances in mitochondrial morphology and calcium handling, associated with the setting of cardiac hypertrophy. Our first finding was that angiotensin-(1-9) can induce mitochondrial fusion through DRP1 phosphorylation. Secondly, angiotensin-(1-9) blocked mitochondrial fission and intracellular calcium dysregulation in a model of norepinephrine-induced cardiomyocyte hypertrophy, preventing the activation of the calcineurin/NFAT signaling pathway. To further investigate angiotensin-(1-9) anti-hypertrophic mechanism, we performed RNA-seq studies, identifying the upregulation of miR-129 under angiotensin-(1-9) treatment. miR-129 decreased the transcript levels of the protein kinase A inhibitor (PKIA), resulting in the activation of the protein kinase A (PKA) signaling pathway. Finally, we showed that PKA activity is necessary for the effects of angiotensin-(1-9) over mitochondrial dynamics, calcium handling and its anti-hypertrophic effects.

This report describes the miRQuest - a novel middleware available in a Web server that allows the end user to do the miRNA research in a user-friendly way. It is known that there are many prediction tools for microRNA (miRNA) identification that use different programming languages and methods to realize this task. It is difficult to understand each tool and apply it to diverse datasets and organisms available for miRNA analysis. miRQuest can easily be used by biologists and researchers with limited experience with bioinformatics. We built it using the middleware architecture on a Web platform for miRNA research that performs two main functions: i) integration of different miRNA prediction tools for miRNA identification in a user-friendly environment; and ii) comparison of these prediction tools. In both cases, the user provides sequences (in FASTA format) as an input set for the analysis and comparisons. All the tools were selected on the basis of a survey of the literature on the available tools for miRNA prediction. As results, three different cases of use of the tools are also described, where one is the miRNA identification analysis in 30 different species. Finally, miRQuest seems to be a novel and useful tool; and it is freely available for both benchmarking and miRNA identification at http://mirquest.integrativebioinformatics.me/.