miR-92a-3p and miR-320a are Upregulated in Plasma Neuron-Derived Extracellular Vesicles of Patients with Frontotemporal Dementia.

Despite the efforts to identify fluid biomarkers to improve diagnosis of Frontotemporal dementia (FTD), only a few candidates have been described in recent years. In a previous study, we identified three circulating miRNAs (miR-92a-3p, miR-320a and miR-320b) differentially expressed in FTD patients with respect to healthy controls and/or Alzheimer's disease (AD) patients. Now, we investigated whether those changes could be due to miRNAs contained in neuron-derived extracellular vesicles (NDEVs).

Plasma microRNA Signature as Companion Diagnostic for Abiraterone Acetate Treatment in Metastatic Castration-Resistant Prostate Cancer: A Pilot Study.

Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study, we explored the potential of circulating microRNAs (c-miRNAs) to stratify patients based on their responsiveness to AA.

HCS-Splice: A High-Content Screening Method to Advance the Discovery of RNA Splicing-Modulating Therapeutics.

Nucleic acid therapeutics have demonstrated an impressive acceleration in recent years. They work through multiple mechanisms of action, including the downregulation of gene expression and the modulation of RNA splicing. While several drugs based on the former mechanism have been approved, few target the latter, despite the promise of RNA splicing modulation.

Identification of miRNAs regulating MAPT expression and their analysis in plasma of patients with dementia.

Background: Dementia is one of the most common diseases in elderly people and hundreds of thousand new cases per year of Alzheimer's disease (AD) are estimated. While the recent decade has seen significant advances in the development of novel biomarkers to identify dementias at their early stage, a great effort has been recently made to identify biomarkers able to improve differential diagnosis. However, only few potential candidates, mainly detectable in cerebrospinal fluid (CSF), have been described so far.

RNA therapeutics for neurological diseases.

Introduction: Ribonucleic acid (RNA) therapeutics are a new class of drugs whose importance is highlighted by the growing number of molecules in the clinic.

Sources Of Data: We focus on RNA therapeutics for neurogenetic disorders, which are broadly defined as diseases with a genetic background and with at least one clinical sign affecting the nervous system. A systematic search identified 14 RNA drugs approved by FDA and many others in development.

miR-18a-5p Is Involved in the Developmental Origin of Prostate Cancer in Maternally Malnourished Offspring Rats: A DOHaD Approach.

The Developmental Origins of Health and Disease (DOHaD) concept correlates early life exposure to stressor conditions with the increased incidence of non-communicable chronic diseases, including prostate cancer (PCa), throughout the life span. However, the molecular mechanisms involved in this process remain poorly understood. In this study, the deregulation of two miRNAs (rno-miR-18a-5p and rno-miR-345-3p) was described in the ventral prostate VP of old rats born to dams fed with a low protein diet (LPD) (6% protein in the diet) during gestational and lactational periods.

News from around the RNA world: new avenues in RNA biology, biotechnology and therapeutics from the 2022 SIBBM meeting.

Since the formalization of the Central Dogma of molecular biology, the relevance of RNA in modulating the flow of information from DNA to proteins has been clear. More recently, the discovery of a vast set of non-coding transcripts involved in crucial aspects of cellular biology has renewed the enthusiasm of the RNA community. Moreover, the remarkable impact of RNA therapies in facing the COVID19 pandemics has bolstered interest in the translational opportunities provided by this incredible molecule.

Exon Skipping Through Chimeric Antisense snRNAs to Correct Retinitis Pigmentosa GTPase-Regulator () Splice Defect.

Inherited retinal dystrophies are caused by mutations in more than 250 genes, each of them carrying several types of mutations that can lead to different clinical phenotypes. Mutations in () cause X-linked Retinitis pigmentosa (RP). A nucleotide substitution in intron 9 of causes the increase of an alternatively spliced isoform of the mature mRNA, bearing exon 9a (E9a).

Identification of miRNAs Bound to an RNA of Interest by MicroRNA Capture Affinity Technology (miR-CATCH).

microRNA capture affinity technology (miR-CATCH) uses affinity capture biotinylated antisense oligonucleotides to co-purify a target transcript together with all its endogenously bound miRNAs. The miR-CATCH assay is performed to investigate miRNAs bound to a specific mRNA. This method allows to have a total vision of miRNAs bound not only to the 3'UTR but also to the 5'UTR and Coding Region of target messenger RNAs (mRNAs).

DNMT3A epigenetically regulates key microRNAs involved in epithelial-to-mesenchymal transition in prostate cancer.

Epithelial-to-mesenchymal transition (EMT) is involved in prostate cancer (PCa) metastatic progression, and its plasticity suggests epigenetic implications. Deregulation of DNA methyltransferases (DNMTs) and several microRNAs (miRNAs) plays a relevant role in EMT, but their interplay has not been clarified yet. In this study, we provide evidence that DNMT3A interaction with several miRNAs has a central role in an ex vivo EMT PCa model obtained via exposure of PC3 cells to conditioned media from cancer-associated fibroblasts.

Delivery of Antisense RNA Therapeutics: Turning Negative Results Into a Positive Development.

The number of novel potential RNA-based antisense therapeutics is rapidly increasing. However, efficient delivery to target tissues is still the main factor that limits their translation into the clinic. Although many groups in academia and industry are working toward the development of methods to improve antisense delivery to overcome this limitation, there are very few coordinated efforts to learn from the experience of other investigators by sharing "negative" results.

MIR-NATs repress MAPT translation and aid proteostasis in neurodegeneration.

The human genome expresses thousands of natural antisense transcripts (NAT) that can regulate epigenetic state, transcription, RNA stability or translation of their overlapping genes. Here we describe MAPT-AS1, a brain-enriched NAT that is conserved in primates and contains an embedded mammalian-wide interspersed repeat (MIR), which represses tau translation by competing for ribosomal RNA pairing with the MAPT mRNA internal ribosome entry site. MAPT encodes tau, a neuronal intrinsically disordered protein (IDP) that stabilizes axonal microtubules.

Delivery of oligonucleotide-based therapeutics: challenges and opportunities.

Nucleic acid-based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues.

Measurements Methods for the Development of MicroRNA-Based Tests for Cancer Diagnosis.

Studies investigating microRNAs as potential biomarkers for cancer, immune-related diseases, or cardiac pathogenic diseases, among others, have exponentially increased in the last years. In particular, altered expression of specific miRNAs correlates with the occurrence of several diseases, making these molecules potential molecular tools for non-invasive diagnosis, prognosis, and response to therapy. Nonetheless, microRNAs are not in clinical use yet, due to inconsistencies in the literature regarding the specific miRNAs identified as biomarkers for a specific disease, which in turn can be attributed to several reasons, including lack of assay standardization and reproducibility.

miR375-3p Distinguishes Low-Grade Neuroendocrine From Non-neuroendocrine Lung Tumors in FFPE Samples.

Lung cancer is still one of the leading cause of death worldwide. The clinical variability of lung cancer is high and drives treatment decision. In this context, correct discrimination of pulmonary neuroendocrine tumors is still of critical relevance.

Upregulation of miR-133b and miR-328 in Patients With Atrial Dilatation: Implications for Stretch-Induced Atrial Fibrillation.

Atrial stretch and dilatation are common features of many clinical conditions predisposing to atrial fibrillation (AF). MicroRNAs (miRs) are emerging as potential molecular determinants of AF, but their relationship with atrial dilatation (AD) is poorly understood. The present study was designed to assess the specific miR expression profiles associated with AD in human atrial tissue.

New Platform for the Direct Profiling of microRNAs in Biofluids.

Circulating microRNAs have been identified as potential biomarkers for early detection, prognosis, and prediction of several diseases. Their use in clinical diagnostics has been limited by the lack of suitable detection techniques. Most of the current technologies suffer from requiring complex protocols, not yet able to deliver robust and cost-effective assays in the field of clinical diagnostics.

Plasma microRNA profiling distinguishes patients with frontotemporal dementia from healthy subjects.

The purpose of this study was to develop an easy and minimally invasive assay to detect a plasma miRNA profile in frontotemporal dementia (FTD) patients, with the final aim of discriminating between FTD patients and healthy controls (HCs). After a global miRNA profiling, significant downregulation of miR-663a, miR-502-3p, and miR-206 (p = 0.0001, p = 0.

Circulating miR-127-3p as a Potential Biomarker for Differential Diagnosis in Frontotemporal Dementia.

Given the heterogeneous nature of frontotemporal dementia (FTD), sensitive biomarkers are greatly needed for the accurate diagnosis of this neurodegenerative disorder. Circulating miRNAs have been reported as promising biomarkers for neurodegenerative disorders and processes affecting the central nervous system, especially in aging. The objective of the study was to evaluate if some circulating miRNAs linked with apoptosis (miR-29b-3p, miR-34a-5p, miR-16-5p, miR-17-5p, miR-107, miR-19b-3p, let-7b-5p, miR-26b-5p, and 127-3p) were able to distinguish between FTD patients and healthy controls.

The short-term impact of probiotic consumption on the oral cavity microbiome.

The dysbiosis of the oral microbiome is associated with both localized and systemic diseases. Modulating the resident microbial communities by the dietary consumption of probiotics has become an appealing means to promote host health by either restoring host-microbe balance or preventing dysbiosis. Most probiotics strategies target the intestinal microbiome, but little is known about their impact on the oral microbiome.

microRNAs Make the Call in Cancer Personalized Medicine.

Since their discovery and the advent of RNA interference, microRNAs have drawn enormous attention because of their ubiquitous involvement in cellular pathways from life to death, from metabolism to communication. It is also widely accepted that they possess an undeniable role in cancer both as tumor suppressors and tumor promoters modulating cell proliferation and migration, epithelial-mesenchymal transition and tumor cell invasion and metastasis. Moreover, microRNAs can even affect the tumor surrounding environment influencing angiogenesis and immune system activation and recruitment.

Delivery is key: lessons learnt from developing splice-switching antisense therapies.

The use of splice-switching antisense therapy is highly promising, with a wealth of pre-clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery.

Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation.

MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached.

Double-target Antisense U1snRNAs Correct Mis-splicing Due to c.639+861C>T and c.639+919G>A GLA Deep Intronic Mutations.

Fabry disease is a rare X-linked lysosomal storage disorder caused by deficiency of the α-galactosidase A (α-Gal A) enzyme, which is encoded by the GLA gene. GLA transcription in humans produces a major mRNA encoding α-Gal A and a minor mRNA of unknown function, which retains a 57-nucleotide-long cryptic exon between exons 4 and 5, bearing a premature termination codon. NM_000169.