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Non-coding RNAs
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Non-coding RNAs

A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Human Genomics and Genetic Diseases".

Deadline for manuscript submissions: closed (31 October 2017) | Viewed by 104457

Special Issue Editors

Prof. Dr. Yan Guo

E-Mail Website
Guest Editor
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Interests: genomics; genetics; bioinformatics; mitochondria
Dr. Shilin Zhao

E-Mail Website
Co-Guest Editor
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
Interests: integrative genomic analysis; genomic data mining; cancer
Dr. Leng Han

E-Mail Website
Co-Guest Editor
Department of Biochemistry and Molecular Biology, UT Health Medical School, Houston, TX 77030, USA
Interests: small RNA; RNA-seq; pathway analysis

Special Issue Information

Dear Colleagues,

Non-coding RNA has gained enormous interest in biomedical research during recent years. More and more researchers are starting to realize that the answers to some diseases may lie outside the coding regions. The National Human Genome Research Institute (NHGRI) launched the ENCODE consortium to study the non-coding regulatory genome, and the consortium claims that 80% of the human genome is associated with some kind of biochemical function through the regulation of the expression of coding genes. Nonetheless, current high throughput technology such as RNA-seq provides us with the opportunity to study non-coding RNA at an unprecedented level.

We invite investigators to contribute original research articles, as well as review articles, that will stimulate the continuing efforts in the research of non-coding RNAs. Manuscripts submitted to this special issue are guaranteed to have a quick and fair review process. Potential topics for the Special Issue include, but are not limited to:

  • Long non-coding RNA
  • Small RNA: miRNA, tRNA, snoRNAs, etc.
  • Pseudogenes
  • Circular RNA
  • Bioinformatics/biostatistics tools related to non-coding RNA
  • Potential functional research of non-coding RNA
  • Disease Association of non-coding RNA

Prof. Yan Guo
Dr. Shilin Zhao
Dr. Leng Han
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Long non-coding RNA
  • Small RNA: miRNA, tRNA, snoRNAs, etc.
  • Pseudogenes
  • Circular RNA
  • Bioinformatics/biostatistics tools related to non-coding RNA
  • Potential functional research of non-coding RNA
  • Disease Association of non-coding RNA

Published Papers (19 papers)

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Research

Jump to: Review

11 pages, 2878 KiB  
Article
miRNA Mediated Noise Making of 3′UTR Mutations in Cancer
by Wei Wu, Lingxiang Wu, Mengyan Zhu, Ziyu Wang, Min Wu, Pengping Li, Yumin Nie, Xue Lin, Jie Hu, Eskil Eskilsson, Qh Wang, Jiaofang Shao and Sali Lyu
Genes 2018, 9(11), 545; https://doi.org/10.3390/genes9110545 - 12 Nov 2018
Cited by 7 | Viewed by 3252
Abstract
Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic [...] Read more.
Somatic mutations in 3′-untranslated regions (3′UTR) do not alter amino acids and are considered to be silent in cancers. We found that such mutations can promote tumor progression by altering microRNA (miRNA) targeting efficiency and consequently affecting miRNA–mRNA interactions. We identified 67,159 somatic mutations located in the 3′UTRs of messenger RNAs (mRNAs) which can alter miRNA–mRNA interactions (functional somatic mutations, funcMutations), and 69.3% of these funcMutations (the degree of energy change > 12 kcal/mol) were identified to significantly promote loss of miRNA-mRNA binding. By integrating mRNA expression profiles of 21 cancer types, we found that the expression of target genes was positively correlated with the loss of absolute affinity level and negatively correlated with the gain of absolute affinity level. Functional enrichment analysis revealed that genes carrying funcMutations were significantly enriched in the MAPK and WNT signaling pathways, and analysis of regulatory modules identified eighteen miRNA modules involved with similar cellular functions. Our findings elucidate a complex relationship between miRNA, mRNA, and mutations, and suggest that 3′UTR mutations may play an important role in tumor development. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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14 pages, 978 KiB  
Article
lncRNA Gene Signatures for Prediction of Breast Cancer Intrinsic Subtypes and Prognosis
by Silu Zhang, Junqing Wang, Torumoy Ghoshal, Dawn Wilkins, Yin-Yuan Mo, Yixin Chen and Yunyun Zhou
Genes 2018, 9(2), 65; https://doi.org/10.3390/genes9020065 - 26 Jan 2018
Cited by 32 | Viewed by 5615
Abstract
Background: Breast cancer is intrinsically heterogeneous and is commonly classified into four main subtypes associated with distinct biological features and clinical outcomes. However, currently available data resources and methods are limited in identifying molecular subtyping on protein-coding genes, and little is known about [...] Read more.
Background: Breast cancer is intrinsically heterogeneous and is commonly classified into four main subtypes associated with distinct biological features and clinical outcomes. However, currently available data resources and methods are limited in identifying molecular subtyping on protein-coding genes, and little is known about the roles of long non-coding RNAs (lncRNAs), which occupies 98% of the whole genome. lncRNAs may also play important roles in subgrouping cancer patients and are associated with clinical phenotypes. Methods: The purpose of this project was to identify lncRNA gene signatures that are associated with breast cancer subtypes and clinical outcomes. We identified lncRNA gene signatures from The Cancer Genome Atlas (TCGA )RNAseq data that are associated with breast cancer subtypes by an optimized 1-Norm SVM feature selection algorithm. We evaluated the prognostic performance of these gene signatures with a semi-supervised principal component (superPC) method. Results: Although lncRNAs can independently predict breast cancer subtypes with satisfactory accuracy, a combined gene signature including both coding and non-coding genes will give the best clinically relevant prediction performance. We highlighted eight potential biomarkers (three from coding genes and five from non-coding genes) that are significantly associated with survival outcomes. Conclusion: Our proposed methods are a novel means of identifying subtype-specific coding and non-coding potential biomarkers that are both clinically relevant and biologically significant. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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15 pages, 9501 KiB  
Article
The Landscape of Small Non-Coding RNAs in Triple-Negative Breast Cancer
by Yan Guo, Hui Yu, Jing Wang, Quanhu Sheng, Shilin Zhao, Ying-Yong Zhao and Brian D. Lehmann
Genes 2018, 9(1), 29; https://doi.org/10.3390/genes9010029 - 10 Jan 2018
Cited by 23 | Viewed by 6137
Abstract
Triple-negative breast cancer (TNBC) is an operational term for breast cancers lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is, therefore, inherently heterogeneous, and is associated with worse prognosis, greater rates of metastasis, and earlier onset. TNBC displays mutational and transcriptional diversity, [...] Read more.
Triple-negative breast cancer (TNBC) is an operational term for breast cancers lacking targetable estrogen receptor expression and HER2 amplifications. TNBC is, therefore, inherently heterogeneous, and is associated with worse prognosis, greater rates of metastasis, and earlier onset. TNBC displays mutational and transcriptional diversity, and distinct mRNA transcriptional subtypes exhibiting unique biology. High-throughput sequencing has extended cancer research far beyond protein coding regions that include non-coding small RNAs, such as miRNA, isomiR, tRNA, snoRNAs, snRNA, yRNA, 7SL, and 7SK. In this study, we performed small RNA profiling of 26 TNBC cell lines, and compared the abundance of non-coding RNAs among the transcriptional subtypes of triple negative breast cancer. We also examined their co-expression pattern with corresponding mRNAs. This study provides a detailed description of small RNA expression in triple-negative breast cancer cell lines that can aid in the development of future biomarker and novel targeted therapies. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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14 pages, 1112 KiB  
Article
Identification of Transposable Elements Contributing to Tissue-Specific Expression of Long Non-Coding RNAs
by Takafumi Chishima, Junichi Iwakiri and Michiaki Hamada
Genes 2018, 9(1), 23; https://doi.org/10.3390/genes9010023 - 09 Jan 2018
Cited by 38 | Viewed by 6611
Abstract
It has been recently suggested that transposable elements (TEs) are re-used as functional elements of long non-coding RNAs (lncRNAs). This is supported by some examples such as the human endogenous retrovirus subfamily H (HERVH) elements contained within lncRNAs and expressed specifically in human [...] Read more.
It has been recently suggested that transposable elements (TEs) are re-used as functional elements of long non-coding RNAs (lncRNAs). This is supported by some examples such as the human endogenous retrovirus subfamily H (HERVH) elements contained within lncRNAs and expressed specifically in human embryonic stem cells (hESCs), as required to maintain hESC identity. There are at least two unanswered questions about all lncRNAs. How many TEs are re-used within lncRNAs? Are there any other TEs that affect tissue specificity of lncRNA expression? To answer these questions, we comprehensively identify TEs that are significantly related to tissue-specific expression levels of lncRNAs. We downloaded lncRNA expression data corresponding to normal human tissue from the Expression Atlas and transformed the data into tissue specificity estimates. Then, Fisher’s exact tests were performed to verify whether the presence or absence of TE-derived sequences influences the tissue specificity of lncRNA expression. Many TE–tissue pairs associated with tissue-specific expression of lncRNAs were detected, indicating that multiple TE families can be re-used as functional domains or regulatory sequences of lncRNAs. In particular, we found that the antisense promoter region of L1PA2, a LINE-1 subfamily, appears to act as a promoter for lncRNAs with placenta-specific expression. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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3124 KiB  
Article
Using Human iPSC-Derived Neurons to Uncover Activity-Dependent Non-Coding RNAs
by Mainá Bitar, Stefanie Kuiper, Elizabeth O’Brien and Guy Barry
Genes 2017, 8(12), 401; https://doi.org/10.3390/genes8120401 - 20 Dec 2017
Cited by 3 | Viewed by 4431
Abstract
Humans are arguably the most complex organisms present on Earth with their ability to imagine, create, and problem solve. As underlying mechanisms enabling these capacities reside in the brain, it is not surprising that the brain has undergone an extraordinary increase in size [...] Read more.
Humans are arguably the most complex organisms present on Earth with their ability to imagine, create, and problem solve. As underlying mechanisms enabling these capacities reside in the brain, it is not surprising that the brain has undergone an extraordinary increase in size and complexity within the last few million years. Human induced pluripotent stem cells (hiPSCs) can be differentiated into many cell types that were virtually inaccessible historically, such as neurons. Here, we used hiPSC-derived neurons to investigate the cellular response to activation at the transcript level. Neuronal activation was performed with potassium chloride (KCl) and its effects were assessed by RNA sequencing. Our results revealed the involvement of long non-coding RNAs and human-specific genetic variants in response to neuronal activation and help validate hiPSCs as a valuable resource for the study of human neuronal networks. In summary, we find that genes affected by KCl-triggered activation are implicated in pathways that drive cell proliferation, differentiation, and the emergence of specialized morphological features. Interestingly, non-coding RNAs of various classes are amongst the most highly expressed genes in activated hiPSC-derived neurons, thus suggesting these play crucial roles in neural pathways and may significantly contribute to the unique functioning of the human brain. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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5475 KiB  
Article
Differential Expression of Serum MicroRNAs Supports CD4+ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma
by Alicja Pacholewska, Matthias F. Kraft, Vincent Gerber and Vidhya Jagannathan
Genes 2017, 8(12), 383; https://doi.org/10.3390/genes8120383 - 12 Dec 2017
Cited by 35 | Viewed by 7569
Abstract
MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising [...] Read more.
MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression analysis. We identified 11 significantly differentially expressed miRNAs between case and control horses: eca-miR-128, eca-miR-744, eca-miR-197, eca-miR-103, eca-miR-107a, eca-miR-30d, eca-miR-140-3p, eca-miR-7, eca-miR-361-3p, eca-miR-148b-3p and eca-miR-215. Pathway enrichment using experimentally validated target genes of the human homologous miRNAs showed a significant enrichment in the regulation of epithelial-to-mesenchymal transition (key player in airway remodeling in asthma) and the phosphatidylinositol (3,4,5)-triphosphate (PIP3) signaling pathway (modulator of CD4+ T cell maturation and function). Downregulated miR-128 and miR-744 supports a Th2/Th17 type immune response in severe equine asthma. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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2171 KiB  
Communication
Phylogenetic Analysis of the SNORD116 Locus
by Matthew A. Kocher and Deborah J. Good
Genes 2017, 8(12), 358; https://doi.org/10.3390/genes8120358 - 30 Nov 2017
Cited by 9 | Viewed by 4209
Abstract
The SNORD116 small nucleolar RNA locus (SNORD116@) is contained within the long noncoding RNA host gene SNHG14 on human chromosome 15q11-q13. The SNORD116 locus is a cluster of 28 or more small nucleolar (sno) RNAs; C/D box (SNORDs). Individual RNAs within [...] Read more.
The SNORD116 small nucleolar RNA locus (SNORD116@) is contained within the long noncoding RNA host gene SNHG14 on human chromosome 15q11-q13. The SNORD116 locus is a cluster of 28 or more small nucleolar (sno) RNAs; C/D box (SNORDs). Individual RNAs within the cluster are tandem, highly similar sequences, referred to as SNORD116-1, SNORD116-2, etc., with the entire set referred to as SNORD116@. There are also related SNORD116 loci on other chromosomes, and these additional loci are conserved among primates. Inherited chromosomal 15q11-q13 deletions, encompassing the SNORD116@ locus, are causative for the paternally-inherited/maternally-imprinted genetic condition, Prader–Willi syndrome (PWS). Using in silico tools, along with molecular-based and sequenced-based confirmation, phylogenetic analysis of the SNORD116@ locus was performed. The consensus sequence for the SNORD116@ snoRNAs from various species was determined both for all the SNORD116 snoRNAs, as well as those grouped using sequence and location according to a human grouping convention. The implications of these findings are put in perspective for studying SNORD116 in patients with inherited Prader–Willi syndrome, as well as model organisms. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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2639 KiB  
Article
Differentially Expressed tRNA-Derived Small RNAs Co-Sediment Primarily with Non-Polysomal Fractions in Drosophila
by Çağdaş Göktaş, Hatice Yiğit, Mehmet İlyas Coşacak and Bünyamin Akgül
Genes 2017, 8(11), 333; https://doi.org/10.3390/genes8110333 - 20 Nov 2017
Cited by 13 | Viewed by 4189
Abstract
Recent studies point to the existence of poorly characterized small regulatory RNAs generated from mRNAs, rRNAs and tRNAs. To explore the subcellular location of tRNA-derived small RNAs, 0–1 and 7–8 h Drosophila embryos were fractionated on sucrose density gradients. Analysis of 12,553,921 deep-sequencing [...] Read more.
Recent studies point to the existence of poorly characterized small regulatory RNAs generated from mRNAs, rRNAs and tRNAs. To explore the subcellular location of tRNA-derived small RNAs, 0–1 and 7–8 h Drosophila embryos were fractionated on sucrose density gradients. Analysis of 12,553,921 deep-sequencing reads from unfractionated and fractionated Drosophila embryos has revealed that tRFs, which are detected mainly from the 5’ends of tRNAs, co-sediment with the non-polysomal fractions. Interestingly, the expression levels of a subset of tRFs change temporally following the maternal-to-zygotic transition in embryos. We detected non-polysomal association of tRFs in S2 cells as well. Differential tRF expression pattern points to developmental significance at the organismal level. These results suggest that tRFs are associated primarily with the non-polysomal complexes in Drosophila embryos and S2 cells. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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1935 KiB  
Article
The HMGA1 Pseudogene 7 Induces miR-483 and miR-675 Upregulation by Activating Egr1 through a ceRNA Mechanism
by Marco De Martino, Giuseppe Palma, Amalia Azzariti, Claudio Arra, Alfredo Fusco and Francesco Esposito
Genes 2017, 8(11), 330; https://doi.org/10.3390/genes8110330 - 17 Nov 2017
Cited by 24 | Viewed by 3938
Abstract
Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role [...] Read more.
Several studies have established that pseudogene mRNAs can work as competing endogenous RNAs and, when deregulated, play a key role in the onset of human neoplasias. Recently, we have isolated two HMGA1 pseudogenes, HMGA1P6 and HMGA1P7. These pseudogenes have a critical role in cancer progression, acting as micro RNA (miRNA) sponges for HMGA1 and other cancer-related genes. HMGA1 pseudogenes were found overexpressed in several human carcinomas, and their expression levels positively correlate with an advanced cancer stage and a poor prognosis. In order to investigate the molecular alterations following HMGA1 pseudogene 7 overexpression, we carried out miRNA sequencing analysis on HMGA1P7 overexpressing mouse embryonic fibroblasts. Intriguingly, the most upregulated miRNAs were miR-483 and miR-675 that have been described as key regulators in cancer progression. Here, we report that HMGA1P7 upregulates miR-483 and miR-675 through a competing endogenous RNA mechanism with Egr1, a transcriptional factor that positively regulates miR-483 and miR-675 expression. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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1767 KiB  
Article
BARHL1 Is Downregulated in Alzheimer’s Disease and May Regulate Cognitive Functions through ESR1 and Multiple Pathways
by Debmalya Barh, María E. García-Solano, Sandeep Tiwari, Antaripa Bhattacharya, Neha Jain, Daniel Torres-Moreno, Belén Ferri, Artur Silva, Vasco Azevedo, Preetam Ghosh, Kenneth Blum, Pablo Conesa-Zamora and George Perry
Genes 2017, 8(10), 245; https://doi.org/10.3390/genes8100245 - 28 Sep 2017
Cited by 12 | Viewed by 5939
Abstract
The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue [...] Read more.
The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue microarray (TMA), we report for the first time that BARHL1 is downregulated in hormone-negative breast cancers and Alzheimer’s disease (AD). Furthermore, using an integrative bioinformatics approach and mining knockout mouse data, we show that: (i) BARHL1 and Estrogen Receptor 1 (ESR1) may constitute a network that regulates Neurotrophin 3 (NTF3)- and Brain Derived Neurotrophic Factor (BDNF)-mediated neurogenesis and neural survival; (ii) this is probably linked to AD pathways affecting aberrant post-translational modifications including SUMOylation and ubiquitination; (iii) the BARHL1-ESR1 network possibly regulates β-amyloid metabolism and memory; and (iv) hsa-mir-18a, having common key targets in the BARHL1-ESR1 network and AD pathway, may modulate neuron death, reduce β-amyloid processing and might also be involved in hearing and cognitive decline associated with AD. We have also hypothesized why estrogen replacement therapy improves AD condition. In addition, we have provided a feasible new mechanism to explain the abnormal function of mossy fibers and cerebellar granule cells related to memory and cognitive decline in AD apart from the Tau and amyloid pathogenesis through our BARHL1-ESR1 axis. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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Review

Jump to: Research

20 pages, 4970 KiB  
Review
The Unforeseen Non-Coding RNAs in Head and Neck Cancer
by Alexandra Iulia Irimie, Alina-Andreea Zimta, Cristina Ciocan, Nikolay Mehterov, Diana Dudea, Cornelia Braicu and Ioana Berindan-Neagoe
Genes 2018, 9(3), 134; https://doi.org/10.3390/genes9030134 - 01 Mar 2018
Cited by 17 | Viewed by 5864
Abstract
Previously ignored non-coding RNAs (ncRNAs) have become the subject of many studies. However, there is an imbalance in the amount of consideration that ncRNAs are receiving. Some transcripts such as microRNAs (miRNAs) or small interfering RNAs (siRNAs) have gained much attention, but it [...] Read more.
Previously ignored non-coding RNAs (ncRNAs) have become the subject of many studies. However, there is an imbalance in the amount of consideration that ncRNAs are receiving. Some transcripts such as microRNAs (miRNAs) or small interfering RNAs (siRNAs) have gained much attention, but it is necessary to investigate other “pieces of the RNA puzzle”. These can offer a more complete view over normal and pathological cell behavior. The other ncRNA species are less studied, either due to their recent discovery, such as stable intronic sequence RNA (sisRNA), YRNA, miRNA-offset RNAs (moRNA), telomerase RNA component (TERC), natural antisense transcript (NAT), transcribed ultraconserved regions (T-UCR), and pseudogene transcript, or because they are still largely seen as non-coding transcripts with no relevance to pathogenesis. Moreover, some are still considered housekeeping RNAs, for instance small nucleolar RNAs (snoRNAs) and TERC. Our review summarizes the biogenesis, mechanism of action and potential role of less known ncRNAs in head and neck cancer, with a particular focus on the installment and progress for this particular cancer type. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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38 pages, 3931 KiB  
Review
Covalent Strategies for Targeting Messenger and Non-Coding RNAs: An Updated Review on siRNA, miRNA and antimiR Conjugates
by Santiago Grijalvo, Adele Alagia, Andreia F. Jorge and Ramon Eritja
Genes 2018, 9(2), 74; https://doi.org/10.3390/genes9020074 - 06 Feb 2018
Cited by 53 | Viewed by 8997
Abstract
Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for modulating gene expression. Antisense oligonucleotides (ASOs) and more recently siRNAs and [...] Read more.
Oligonucleotide-based therapy has become an alternative to classical approaches in the search of novel therapeutics involving gene-related diseases. Several mechanisms have been described in which demonstrate the pivotal role of oligonucleotide for modulating gene expression. Antisense oligonucleotides (ASOs) and more recently siRNAs and miRNAs have made important contributions either in reducing aberrant protein levels by sequence-specific targeting messenger RNAs (mRNAs) or restoring the anomalous levels of non-coding RNAs (ncRNAs) that are involved in a good number of diseases including cancer. In addition to formulation approaches which have contributed to accelerate the presence of ASOs, siRNAs and miRNAs in clinical trials; the covalent linkage between non-viral vectors and nucleic acids has also added value and opened new perspectives to the development of promising nucleic acid-based therapeutics. This review article is mainly focused on the strategies carried out for covalently modifying siRNA and miRNA molecules. Examples involving cell-penetrating peptides (CPPs), carbohydrates, polymers, lipids and aptamers are discussed for the synthesis of siRNA conjugates whereas in the case of miRNA-based drugs, this review article makes special emphasis in using antagomiRs, locked nucleic acids (LNAs), peptide nucleic acids (PNAs) as well as nanoparticles. The biomedical applications of siRNA and miRNA conjugates are also discussed. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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11 pages, 645 KiB  
Review
Long Non-Coding RNAs in Multiple Myeloma
by Lucia Nobili, Domenica Ronchetti, Luca Agnelli, Elisa Taiana, Cristina Vinci and Antonino Neri
Genes 2018, 9(2), 69; https://doi.org/10.3390/genes9020069 - 01 Feb 2018
Cited by 22 | Viewed by 4622
Abstract
Multiple myeloma (MM) is an incurable disease caused by the malignant proliferation of bone marrow plasma cells, whose pathogenesis remains largely unknown. Although a large fraction of the genome is actively transcribed, most of the transcripts do not serve as templates for proteins [...] Read more.
Multiple myeloma (MM) is an incurable disease caused by the malignant proliferation of bone marrow plasma cells, whose pathogenesis remains largely unknown. Although a large fraction of the genome is actively transcribed, most of the transcripts do not serve as templates for proteins and are referred to as non-coding RNAs (ncRNAs), broadly divided into short and long transcripts on the basis of a 200-nucleotide threshold. Short ncRNAs, especially microRNAs, have crucial roles in virtually all types of cancer, including MM, and have gained importance in cancer diagnosis and prognosis, predicting the response to therapy and, notably, as innovative therapeutic targets. Long ncRNAs (lncRNAs) are a very heterogeneous group, involved in many physiological cellular and genomic processes as well as in carcinogenesis, cancer metastasis, and invasion. LncRNAs are aberrantly expressed in various types of cancers, including hematological malignancies, showing either oncogenic or tumor suppressive functions. However, the mechanisms of the related disease-causing events are not yet revealed in most cases. Besides emerging as key players in cancer initiation and progression, lncRNAs own many interesting features as biomarkers with diagnostic and prognostic importance and, possibly, for their utility in therapeutic terms as druggable molecules. This review focuses on the role of lncRNAs in the pathogenesis of MM and summarizes the recent literature. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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23 pages, 621 KiB  
Review
MiRNA Influences in Neuroblast Modulation: An Introspective Analysis
by Vanessa Zammit, Byron Baron and Duncan Ayers
Genes 2018, 9(1), 26; https://doi.org/10.3390/genes9010026 - 09 Jan 2018
Cited by 9 | Viewed by 4123
Abstract
Neuroblastoma (NB) is the most common occurring solid paediatric cancer in children under the age of five years. Whether of familial or sporadic origin, chromosome abnormalities contribute to the development of NB and cause dysregulation of microRNAs (miRNAs). MiRNAs are small non-coding, single [...] Read more.
Neuroblastoma (NB) is the most common occurring solid paediatric cancer in children under the age of five years. Whether of familial or sporadic origin, chromosome abnormalities contribute to the development of NB and cause dysregulation of microRNAs (miRNAs). MiRNAs are small non-coding, single stranded RNAs that target messenger RNAs at the post-transcriptional levels by repressing translation within all facets of human physiology. Such gene ‘silencing’ activities by miRNAs allows the development of regulatory feedback loops affecting multiple functions within the cell, including the possible differentiation of neural stem cell (NSC) lineage selection. Neurogenesis includes stages of self-renewal and fate specification of NSCs, migration and maturation of young neurones, and functional integration of new neurones into the neural circuitry, all of which are regulated by miRNAs. The role of miRNAs and their interaction in cellular processes are recognised aspects of cancer genetics, and miRNAs are currently employed as biomarkers for prognosis and tumour characterisation in multiple cancer models. Consequently, thorough understanding of the mechanisms of how these miRNAs interplay at the transcriptomic level will definitely lead to the development of novel, bespoke and efficient therapeutic measures, with this review focusing on the influences of miRNAs on neuroblast modulations leading to neuroblastoma. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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14 pages, 565 KiB  
Review
Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells
by Sarah Inwood, Michael J. Betenbaugh and Joseph Shiloach
Genes 2018, 9(1), 25; https://doi.org/10.3390/genes9010025 - 09 Jan 2018
Cited by 9 | Viewed by 4960
Abstract
The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO) cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK), while not being as widely used as CHO [...] Read more.
The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO) cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK), while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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1634 KiB  
Review
Current Research on Non-Coding Ribonucleic Acid (RNA)
by Jing Wang, David C. Samuels, Shilin Zhao, Yu Xiang, Ying-Yong Zhao and Yan Guo
Genes 2017, 8(12), 366; https://doi.org/10.3390/genes8120366 - 05 Dec 2017
Cited by 53 | Viewed by 7464
Abstract
Non-coding ribonucleic acid (RNA) has without a doubt captured the interest of biomedical researchers. The ability to screen the entire human genome with high-throughput sequencing technology has greatly enhanced the identification, annotation and prediction of the functionality of non-coding RNAs. In this review, [...] Read more.
Non-coding ribonucleic acid (RNA) has without a doubt captured the interest of biomedical researchers. The ability to screen the entire human genome with high-throughput sequencing technology has greatly enhanced the identification, annotation and prediction of the functionality of non-coding RNAs. In this review, we discuss the current landscape of non-coding RNA research and quantitative analysis. Non-coding RNA will be categorized into two major groups by size: long non-coding RNAs and small RNAs. In long non-coding RNA, we discuss regular long non-coding RNA, pseudogenes and circular RNA. In small RNA, we discuss miRNA, transfer RNA, piwi-interacting RNA, small nucleolar RNA, small nuclear RNA, Y RNA, single recognition particle RNA, and 7SK RNA. We elaborate on the origin, detection method, and potential association with disease, putative functional mechanisms, and public resources for these non-coding RNAs. We aim to provide readers with a complete overview of non-coding RNAs and incite additional interest in non-coding RNA research. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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Review
Non-Coding RNAs in Pediatric Airway Diseases
by Beata Narożna, Wojciech Langwiński and Aleksandra Szczepankiewicz
Genes 2017, 8(12), 348; https://doi.org/10.3390/genes8120348 - 27 Nov 2017
Cited by 34 | Viewed by 4421
Abstract
Non-coding RNAs (ncRNAs) are involved in the regulation of numerous biological processes and pathways and therefore have been extensively studied in human diseases. Previous reports have shown that non-coding RNAs play a crucial role in the pathogenesis and aberrant regulation of respiratory diseases. [...] Read more.
Non-coding RNAs (ncRNAs) are involved in the regulation of numerous biological processes and pathways and therefore have been extensively studied in human diseases. Previous reports have shown that non-coding RNAs play a crucial role in the pathogenesis and aberrant regulation of respiratory diseases. The altered expression of microRNAs (miRNAs) and long non-coding RNAs in blood and also locally in sputum or exhaled breath condensate influences lung function, immune response, and disease phenotype and may be used for the development of biomarkers specific for airway disease. In this review, we provide an overview of the recent works studying the non-coding RNAs in airway diseases, with a particular focus on chronic respiratory diseases of childhood. We have chosen the most common chronic respiratory condition—asthma—and the most severe, chronic disease of the airways—cystic fibrosis. Study of the altered expression of non-coding RNAs in these diseases may be key to better understanding their pathogenesis and improving diagnosis, while also holding promise for the development of therapeutic strategies using the regulatory potential of non-coding RNAs. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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Review
Circulating microRNAs and Bioinformatics Tools to Discover Novel Diagnostic Biomarkers of Pediatric Diseases
by Antonella Baldassarre, Cristina Felli, Giorgio Prantera and Andrea Masotti
Genes 2017, 8(9), 234; https://doi.org/10.3390/genes8090234 - 19 Sep 2017
Cited by 31 | Viewed by 5696
Abstract
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Current studies have shown that miRNAs are also present in extracellular spaces, packaged into various membrane-bound vesicles, or associated with RNA-binding proteins. Circulating miRNAs are highly stable and can [...] Read more.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the post-transcriptional level. Current studies have shown that miRNAs are also present in extracellular spaces, packaged into various membrane-bound vesicles, or associated with RNA-binding proteins. Circulating miRNAs are highly stable and can act as intercellular messengers to affect many physiological processes. MicroRNAs circulating in body fluids have generated strong interest in their potential use as clinical biomarkers. In fact, their remarkable stability and the relative ease of detection make circulating miRNAs ideal tools for rapid and non-invasive diagnosis. This review summarizes recent insights about the origin, functions and diagnostic potential of extracellular miRNAs by especially focusing on pediatric diseases in order to explore the feasibility of alternative sampling sources for the development of non-invasive pediatric diagnostics. We will also discuss specific bioinformatics tools and databases for circulating miRNAs focused on the identification and discovery of novel diagnostic biomarkers of pediatric diseases. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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Review
Long Noncoding RNAs as Diagnostic and Therapeutic Targets in Type 2 Diabetes and Related Complications
by Fatjon Leti and Johanna K. DiStefano
Genes 2017, 8(8), 207; https://doi.org/10.3390/genes8080207 - 22 Aug 2017
Cited by 69 | Viewed by 5299
Abstract
Protein-coding genes represent only a small fraction of the human genome. In the past, the majority of the genomic sequence has been considered transcriptionally silent, but recent large-scale studies have uncovered an array of functionally significant elements, including non-protein-coding transcripts, within these noncoding [...] Read more.
Protein-coding genes represent only a small fraction of the human genome. In the past, the majority of the genomic sequence has been considered transcriptionally silent, but recent large-scale studies have uncovered an array of functionally significant elements, including non-protein-coding transcripts, within these noncoding regions of the human genome. Long noncoding RNAs (lncRNAs), a class of noncoding transcripts with lengths >200 nucleotides, are pervasively transcribed in the genome and function as signals, decoys, guides, or scaffolds to regulate gene expression. More than 200 diseases have been associated with dysregulated or dysfunctional lncRNAs, and new associations continue to accumulate in the literature. The role of lncRNAs in the pathogenesis of type 2 diabetes mellitus and related complications has only recently been recognized, but there is already evidence for their involvement in many of the pathophysiological mechanisms underlying the disease. In this review, we summarize the current knowledge of the functions and underlying mechanisms of lncRNA activity with a focus on type 2 diabetes mellitus and related renal and retinal complications of the disease. We also discuss the potential of lncRNAs to serve as therapeutic targets for drug development and diagnostic markers for clinical applications in the management of diabetes. Full article
(This article belongs to the Special Issue Non-coding RNAs)
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