MicroRNAs and Long Non-coding RNAs in Genetic Diseases

Abstract

Since the discovery and classification of non-coding RNAs, their roles have gained great attention. In this respect, microRNAs and long non-coding RNAs have been firmly demonstrated to be linked to regulation of gene expression and onset of human diseases, including rare genetic diseases; therefore they are suitable targets for therapeutic intervention. This issue, in the context of rare genetic diseases, is being considered by an increasing number of research groups and is of key interest to the health community. In the case of rare genetic diseases, the possibility of developing personalized therapy in precision medicine has attracted the attention of researchers and clinicians involved in developing “orphan medicinal products” and proposing these to the European Medicines Agency (EMA) and to the Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD) in the United States. The major focuses of these activities are the evaluation and development of products (drugs, biologics, devices, or medical foods) considered to be promising for diagnosis and/or treatment of rare diseases or conditions, including rare genetic diseases. In an increasing number of rare genetic diseases, analysis of microRNAs and long non-coding RNAs has been proven a promising strategy. These diseases include, but are not limited to, Duchenne muscular dystrophy, cystic fibrosis, Rett syndrome, and β-thalassemia. In conclusion, a large number of approaches based on targeting microRNAs and long non-coding RNAs are expected in the field of molecular diagnosis and therapy, with a facilitated technological transfer in the case of rare genetic diseases, in virtue of the existing regulation concerning these diseases.

Duchenne Muscular Dystrophy (DMD) Diagnosis: Past and Present Perspectives

“…MiRNAs act through binding to a specific region in the 3 0 -UTR in the target mRNA molecules, thus, inducing mRNA degradation and inhibiting the translation process [42]. The circulating levels of miRNAs in serum reflect the intracellular status and hence, they are excellent biomarkers for many pathological conditions as they can be detected from liquid biopsies and/or tissue specimens [43]. Many studies attempted to study the modulation in the levels of different miRNAs ( Table 2).…”

A Peptide Nucleic Acid (PNA) Masking the miR-145-5p Binding Site of the 3′UTR of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mRNA Enhances CFTR Expression in Calu-3 Cells

“…Epigenetic regulation of expression of cystic fibrosis transmembrane conductance regulator (CFTR) gene by miRNAs has been recently reported by different groups [24][25][26][27][28][29][30][31][32][33][34]. For instance, expression of miR-145 and miR-494 was found to anti-regulate CFTR [28].…”

Theranostics of Genetic Diseases

“…For this reason, the term 'theranostics' has been proposed-combining 'therapeutic strategies' and 'diagnostics' within the same term. Four articles in this issue review therapeutic approaches, discussing the issue of gene therapy [1], gene editing [2,3], and micro-RNA (miRNA) therapeutics [4]. Ghiaccio et al [1] review gene therapy for β-thalassemia with respect to the milestones reached, novel developments, and present (and future) challenges.…”

“…Growing interest appears to be associated with novel markers and molecular targets, which might lead to implementation of the therapeutic protocols in pre-clinical studies. In this respect, the network constituted by transcription factors and non-coding RNAs (ncRNAs; including miRNAs) might be of great interest in the regulation of gene expression in genetic diseases, as described by Finotti et al [4]. In fact, since their discovery and classification, the roles of ncR-NAs have gained great attention in genetic diseases, and both miRNAs and long ncRNAs (lncRNAs) can be considered excellent markers for advanced diagnostic protocols and suitable targets for therapeutic interventions [14][15][16][17].…”

“…In this respect, both anti-miRNA molecules or miRNA mimicking strategies might be of interest [14]. The review by Finotti et al [4] points to the regulation of the γ-globin transcriptional repressor as a possible key element to be modified to obtain clinically relevant outcomes in β-thalassemia and other hemoglobinopathies. This article should be considered together with the papers by Katsantoni [18] (Omics as a tool for identification of novel biomarkers associated to β-thalassemia) and Menzel and Thein [19] (describing gene modifiers in sickle-cell disease).…”