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Topical Collection "Feature Papers in Non-coding RNA"

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A topical collection in Non-Coding RNA (ISSN 2311-553X).

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Editor

Prof. Dr. George A Calin
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Guest Editor

Department of Translational Molecular Pathology, Center for RNA Interference and Non-coding RNAs, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: non-coding RNA; microRNA; cancer; metastasis
Special Issues, Collections and Topics in MDPI journals

Topical Collection Information

Dear Colleagues,

This Topical Collection “Feature Papers in Non-coding RNA” aims to collect high-quality research articles, review articles, and communications in all the fields of non-coding RNA research and their regulatory roles. Since the aim of this Topical Collection is to illustrate, through selected works, frontier research in noncoding RNA, we encourage Editorial Board Members of Non-coding RNA to contribute papers reflecting the latest progress in their research field, or relevant experts and colleagues to do so. Please kindly note that only invited papers can be published online once accepted in this collection.

Topics include, without being limited to, the following:

Functional studies dealing with the identification, structure–function relationships, or biological activity of miRNAs, siRNAs, piRNAs, tRNAs, long noncoding RNAs, and other classes of RNAs;

Analysis of RNA processing, RNA binding proteins, RNA signaling, and RNA interaction pathways;

RNA analyses, informatics, tools, and technologies;

Translational studies involving long and short noncoding RNAs.

Prof. Dr. Georges A Calin
Guest Editor

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 collection 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. Non-Coding RNA is an international peer-reviewed open access semimonthly 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 1600 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.

Published Papers (23 papers)

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2022

Jump to: 2021, 2020

Open AccessArticle

Direct Comparison of Chol-siRNA Polyplexes and Chol-DsiRNA Polyplexes Targeting STAT3 in a Syngeneic Murine Model of TNBC

Zhen Ye

Mai Mohamed Abdelmoaty

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Non-Coding RNA 2022, 8(1), 8; https://doi.org/10.3390/ncrna8010008 - 13 Jan 2022

Viewed by 1124

Abstract

RNA interference (RNAi) molecules have tremendous potential for cancer therapy but are limited by insufficient potency after intravenous (IV) administration. We previously found that polymer complexes (polyplexes) formed between 3′-cholesterol-modified siRNA (Chol-siRNA) or DsiRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase RNAi potency against stably expressed LUC mRNA in primary syngeneic murine breast tumors after daily IV dosing. Chol-DsiRNA polyplexes, however, maintain LUC mRNA suppression for ~48 h longer after the final dose than Chol-siRNA polyplexes, which suggests that they are the better candidate formulation. Here, we directly compared the activities of Chol-siRNA polyplexes and Chol-DsiRNA polyplexes in primary murine 4T1 breast tumors against STAT3, a therapeutically relevant target gene that is overexpressed in many solid tumors, including breast cancer. We found that Chol-siSTAT3 polyplexes suppressed STAT3 mRNA in 4T1 tumors with similar potency (half-maximal ED₅₀ 0.3 mg/kg) and kinetics (over 96 h) as Chol-DsiSTAT3 polyplexes, but with slightly lower activity against total Stat3 protein (29% vs. 42% suppression) and tumor growth (11.5% vs. 8.6% rate-based T/C ratio) after repeated IV administration of equimolar, tumor-saturating doses every other day. Thus, both Chol-siRNA polyplexes and Chol-DsiRNA polyplexes may be suitable clinical candidates for the RNAi therapy of breast cancer and other solid tumors. Full article

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2021

Jump to: 2022, 2020

Open AccessFeature PaperReview

Cooperativity and Interdependency between RNA Structure and RNA–RNA Interactions

Ilias Skeparnias

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Jinwei Zhang

Non-Coding RNA 2021, 7(4), 81; https://doi.org/10.3390/ncrna7040081 - 15 Dec 2021

Cited by 1 | Viewed by 1606

Abstract

Complex RNA–RNA interactions are increasingly known to play key roles in numerous biological processes from gene expression control to ribonucleoprotein granule formation. By contrast, the nature of these interactions and characteristics of their interfaces, especially those that involve partially or wholly structured RNAs, remain elusive. Herein, we discuss different modalities of RNA–RNA interactions with an emphasis on those that depend on secondary, tertiary, or quaternary structure. We dissect recently structurally elucidated RNA–RNA complexes including RNA triplexes, riboswitches, ribozymes, and reverse transcription complexes. These analyses highlight a reciprocal relationship that intimately links RNA structure formation with RNA–RNA interactions. The interactions not only shape and sculpt RNA structures but also are enabled and modulated by the structures they create. Understanding this two-way relationship between RNA structure and interactions provides mechanistic insights into the expanding repertoire of noncoding RNA functions, and may inform the design of novel therapeutics that target RNA structures or interactions. Full article

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Open AccessReview

Non-Coding Variants in Cancer: Mechanistic Insights and Clinical Potential for Personalized Medicine

Marios Lange

Rodiola Begolli

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Antonis Giakountis

Non-Coding RNA 2021, 7(3), 47; https://doi.org/10.3390/ncrna7030047 - 02 Aug 2021

Cited by 2 | Viewed by 2289

Abstract

The cancer genome is characterized by extensive variability, in the form of Single Nucleotide Polymorphisms (SNPs) or structural variations such as Copy Number Alterations (CNAs) across wider genomic areas. At the molecular level, most SNPs and/or CNAs reside in non-coding sequences, ultimately affecting the regulation of oncogenes and/or tumor-suppressors in a cancer-specific manner. Notably, inherited non-coding variants can predispose for cancer decades prior to disease onset. Furthermore, accumulation of additional non-coding driver mutations during progression of the disease, gives rise to genomic instability, acting as the driving force of neoplastic development and malignant evolution. Therefore, detection and characterization of such mutations can improve risk assessment for healthy carriers and expand the diagnostic and therapeutic toolbox for the patient. This review focuses on functional variants that reside in transcribed or not transcribed non-coding regions of the cancer genome and presents a collection of appropriate state-of-the-art methodologies to study them. Full article

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Open AccessReview

Emerging Role of MicroRNA-200 Family in Dentistry

Pei-Ling Hsieh

Chun-Chung Huang

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Cheng-Chia Yu

Non-Coding RNA 2021, 7(2), 35; https://doi.org/10.3390/ncrna7020035 - 11 Jun 2021

Viewed by 2412

Abstract

MicroRNAs (miRNAs) are endogenous non-coding RNAs ~22 nucleotides in length, which have been shown to participate in various biological processes. As one of the most researched miRNAs, the miR-200 family has been found to regulate several factors that are associated with the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs) behavior. In this review, we briefly summarize the background of the miR-200 family and their implication in various dental diseases. We focus on the expression changes, biological functions, and clinical significance of the miR-200 family in oral cancer; periodontitis; oral potentially malignant disorder; gingival overgrowth; and other periodontal diseases. Additionally, we discuss the use of the miR-200 family as molecular biomarkers for diagnosis, prognostic, and therapeutic application. Full article

Open AccessArticle

Global Analysis of RNA-Dependent RNA Polymerase-Dependent Small RNAs Reveals New Substrates and Functions for These Proteins and SGS3 in Arabidopsis

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Non-Coding RNA 2021, 7(2), 28; https://doi.org/10.3390/ncrna7020028 - 27 Apr 2021

Cited by 2 | Viewed by 2771

Abstract

RNA silencing pathways control eukaryotic gene expression transcriptionally or posttranscriptionally in a sequence-specific manner. In RNA silencing, the production of double-stranded RNA (dsRNA) gives rise to various classes of 20–24 nucleotide (nt) small RNAs (smRNAs). In Arabidopsis thaliana, smRNAs are often derived from long dsRNA molecules synthesized by one of the six genomically encoded RNA-dependent RNA Polymerase (RDR) proteins. However, the full complement of the RDR-dependent smRNAs and functions that these proteins and their RNA-binding cofactors play in plant RNA silencing has not been fully uncovered. To address this gap, we performed a global genomic analysis of all six RDRs and two of their cofactors to find new substrates for RDRs and targets of the resulting RDR-derived siRNAs to uncover new functions for these proteins in plants. Based on these analyses, we identified substrates for the three RDRγ clade proteins (RDR3–5), which had not been well-characterized previously. We also identified new substrates for the other three RDRs (RDR1, RDR2, and RDR6) as well as the RDR2 cofactor RNA-directed DNA methylation 12 (RDM12) and the RDR6 cofactor suppressor of gene silencing 3 (SGS3). These findings revealed that the target substrates of SGS3 are not limited to those solely utilized by RDR6, but that this protein seems to be a more general cofactor for the RDR family of proteins. Additionally, we found that RDR6 and SGS3 are involved in the production of smRNAs that target transcripts related to abiotic stresses, including water deprivation, salt stress, and ABA response, and as expected the levels of these mRNAs are increased in rdr6 and sgs3 mutant plants. Correspondingly, plants that lack these proteins (rdr6 and sgs3 mutants) are hypersensitive to ABA treatment, tolerant to high levels of PEG8000, and have a higher survival rate under salt treatment in comparison to wild-type plants. In total, our analyses have provided an extremely data-rich resource for uncovering new functions of RDR-dependent RNA silencing in plants, while also revealing a previously unexplored link between the RDR6/SGS3-dependent pathway and plant abiotic stress responses. Full article

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Graphical abstract

Open AccessReview

MicroRNAs as Candidate Biomarkers for Alzheimer’s Disease

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Non-Coding RNA 2021, 7(1), 8; https://doi.org/10.3390/ncrna7010008 - 01 Feb 2021

Cited by 6 | Viewed by 2724

Abstract

The neurological damage of Alzheimer’s disease (AD) is thought to be irreversible upon onset of dementia-like symptoms, as it takes years to decades for occult pathologic changes to become symptomatic. It is thus necessary to identify individuals at risk for the development of the disease before symptoms manifest in order to provide early intervention. Surrogate markers are critical for early disease detection, stratification of patients in clinical trials, prediction of disease progression, evaluation of response to treatment, and also insight into pathomechanisms. Here, we review the evidence for a number of microRNAs that may serve as biomarkers with possible mechanistic insights into the AD pathophysiologic processes, years before the clinical manifestation of the disease. Full article

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Open AccessFeature PaperReview

Exosomes in Immune Regulation

Heidi Schwarzenbach

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Peter B. Gahan

Non-Coding RNA 2021, 7(1), 4; https://doi.org/10.3390/ncrna7010004 - 08 Jan 2021

Cited by 7 | Viewed by 3087

Abstract

Exosomes, small extracellular vesicles mediate intercellular communication by transferring their cargo including DNA, RNA, proteins and lipids from cell to cell. Notably, in the immune system, they have protective functions. However in cancer, exosomes acquire new, immunosuppressive properties that cause the dysregulation of immune cells and immune escape of tumor cells supporting cancer progression and metastasis. Therefore, current investigations focus on the regulation of exosome levels for immunotherapeutic interventions. In this review, we discuss the role of exosomes in immunomodulation of lymphoid and myeloid cells, and their use as immune stimulatory agents to elicit specific cytotoxic responses against the tumor. Full article

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2020

Jump to: 2022, 2021

Open AccessArticle

Non-Coding RNAs as Prognostic Biomarkers: A miRNA Signature Specific for Aggressive Early-Stage Lung Adenocarcinomas

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Non-Coding RNA 2020, 6(4), 48; https://doi.org/10.3390/ncrna6040048 - 15 Dec 2020

Cited by 3 | Viewed by 2778

Abstract

Lung cancer burden can be reduced by adopting primary and secondary prevention strategies such as anti-smoking campaigns and low-dose CT screening for high risk subjects (aged >50 and smokers >30 packs/year). Recent CT screening trials demonstrated a stage-shift towards earlier stage lung cancer and reduction of mortality (~20%). However, a sizable fraction of patients (30–50%) with early stage disease still experience relapse and an adverse prognosis. Thus, the identification of effective prognostic biomarkers in stage I lung cancer is nowadays paramount. Here, we applied a multi-tiered approach relying on coupled RNA-seq and miRNA-seq data analysis of a large cohort of lung cancer patients (TCGA-LUAD, n = 510), which enabled us to identify prognostic miRNA signatures in stage I lung adenocarcinoma. Such signatures showed high accuracy (AUC ranging between 0.79 and 0.85) in scoring aggressive disease. Importantly, using a network-based approach we rewired miRNA-mRNA regulatory networks, identifying a minimal signature of 7 miRNAs, which was validated in a cohort of FFPE lung adenocarcinoma samples (CSS, n = 44) and controls a variety of genes overlapping with cancer relevant pathways. Our results further demonstrate the reliability of miRNA-based biomarkers for lung cancer prognostication and make a step forward to the application of miRNA biomarkers in the clinical routine. Full article

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Open AccessReview

Emerging Roles of Long Noncoding RNAs in the Cytoplasmic Milieu

Michelle Aillaud

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Leon N Schulte

Non-Coding RNA 2020, 6(4), 44; https://doi.org/10.3390/ncrna6040044 - 09 Nov 2020

Cited by 13 | Viewed by 3431

Abstract

While the important functions of long noncoding RNAs (lncRNAs) in nuclear organization are well documented, their orchestrating and architectural roles in the cytoplasmic environment have long been underestimated. However, recently developed fractionation and proximity labelling approaches have shown that a considerable proportion of cellular lncRNAs is exported into the cytoplasm and associates nonrandomly with proteins in the cytosol and organelles. The functions of these lncRNAs range from the control of translation and mitochondrial metabolism to the anchoring of cellular components on the cytoskeleton and regulation of protein degradation at the proteasome. In the present review, we provide an overview of the functions of lncRNAs in cytoplasmic structures and machineries und discuss their emerging roles in the coordination of the dense intracellular milieu. It is becoming apparent that further research into the functions of these lncRNAs will lead to an improved understanding of the spatiotemporal organization of cytoplasmic processes during homeostasis and disease. Full article

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Open AccessReview

Involvement of Long Non-Coding RNAs (lncRNAs) in Tumor Angiogenesis

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Non-Coding RNA 2020, 6(4), 42; https://doi.org/10.3390/ncrna6040042 - 25 Sep 2020

Cited by 17 | Viewed by 3468

Abstract

Long non-coding RNAs (lncRNAs) are defined as non-protein coding transcripts with a minimal length of 200 nucleotides. They are involved in various biological processes such as cell differentiation, apoptosis, as well as in pathophysiological processes. Numerous studies considered that frequently deregulated lncRNAs contribute to all hallmarks of cancer including metastasis, drug resistance, and angiogenesis. Angiogenesis, the formation of new blood vessels, is crucial for a tumor to receive sufficient amounts of nutrients and oxygen and therefore, to grow and exceed in its size over the diameter of 2 mm. In this review, the regulatory mechanisms of lncRNAs are described, which influence tumor angiogenesis by directly or indirectly regulating oncogenic pathways, interacting with other transcripts such as microRNAs (miRNAs) or modulating the tumor microenvironment. Further, angiogenic lncRNAs occurring in several cancer types such as liver, gastrointestinal cancer, or brain tumors are summarized. Growing evidence on the influence of lncRNAs on tumor angiogenesis verified these transcripts as potential predictive or diagnostic biomarkers or therapeutic targets of anti-angiogenesis treatment. However, there are many unsolved questions left which are pointed out in this review, hence driving comprehensive research in this area is necessary to enable an effective use of lncRNAs as either therapeutic molecules or diagnostic targets in cancer. Full article

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Open AccessReview

Non-Coding RNAs in Multiple Myeloma Bone Disease Pathophysiology

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Non-Coding RNA 2020, 6(3), 37; https://doi.org/10.3390/ncrna6030037 - 09 Sep 2020

Cited by 6 | Viewed by 3257

Abstract

Bone remodeling is uncoupled in the multiple myeloma (MM) bone marrow niche, resulting in enhanced osteoclastogenesis responsible of MM-related bone disease (MMBD). Several studies have disclosed the mechanisms underlying increased osteoclast formation and activity triggered by the various cellular components of the MM bone marrow microenvironment, leading to the identification of novel targets for therapeutic intervention. In this regard, recent attention has been given to non-coding RNA (ncRNA) molecules, that finely tune gene expression programs involved in bone homeostasis both in physiological and pathological settings. In this review, we will analyze major signaling pathways involved in MMBD pathophysiology, and report emerging evidence of their regulation by different classes of ncRNAs. Full article

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Open AccessPerspective

Genesis of Non-Coding RNA Genes in Human Chromosome 22—A Sequence Connection with Protein Genes Separated by Evolutionary Time

Nicholas Delihas

Non-Coding RNA 2020, 6(3), 36; https://doi.org/10.3390/ncrna6030036 - 03 Sep 2020

Cited by 3 | Viewed by 2812

Abstract

A small phylogenetically conserved sequence of 11,231 bp, termed FAM247, is repeated in human chromosome 22 by segmental duplications. This sequence forms part of diverse genes that span evolutionary time, the protein genes being the earliest as they are present in zebrafish and/or mice genomes, and the long noncoding RNA genes and pseudogenes the most recent as they appear to be present only in the human genome. We propose that the conserved sequence provides a nucleation site for new gene development at evolutionarily conserved chromosomal loci where the FAM247 sequences reside. The FAM247 sequence also carries information in its open reading frames that provides protein exon amino acid sequences; one exon plays an integral role in immune system regulation, specifically, the function of ubiquitin-specific protease (USP18) in the regulation of interferon. An analysis of this multifaceted sequence and the genesis of genes that contain it is presented. Full article

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Open AccessFeature PaperReview

Non-Coding RNA Databases in Cardiovascular Research

Deepak Balamurali

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Monika Stoll

Non-Coding RNA 2020, 6(3), 35; https://doi.org/10.3390/ncrna6030035 - 02 Sep 2020

Cited by 7 | Viewed by 3994

Abstract

Cardiovascular diseases (CVDs) are of multifactorial origin and can be attributed to several genetic and environmental components. CVDs are the leading cause of mortality worldwide and they primarily damage the heart and the vascular system. Non-coding RNA (ncRNA) refers to functional RNA molecules, which have been transcribed into DNA but do not further get translated into proteins. Recent transcriptomic studies have identified the presence of thousands of ncRNA molecules across species. In humans, less than 2% of the total genome represents the protein-coding genes. While the role of many ncRNAs is yet to be ascertained, some long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been associated with disease progression, serving as useful diagnostic and prognostic biomarkers. A plethora of data repositories specialized in ncRNAs have been developed over the years using publicly available high-throughput data from next-generation sequencing and other approaches, that cover various facets of ncRNA research like basic and functional annotation, expressional profile, structural and molecular changes, and interaction with other biomolecules. Here, we provide a compendium of the current ncRNA databases relevant to cardiovascular research. Full article

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Open AccessFeature PaperReview

Long Non-Coding RNAs in Liver Cancer and Nonalcoholic Steatohepatitis

Shizuka Uchida

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Sakari Kauppinen

Non-Coding RNA 2020, 6(3), 34; https://doi.org/10.3390/ncrna6030034 - 29 Aug 2020

Cited by 7 | Viewed by 3024

Abstract

This review aims to highlight the recent findings of long non-coding RNAs (lncRNAs) in liver disease. In particular, we focus on the functions of lncRNAs in hepatocellular carcinoma (HCC) and non-alcoholic steatohepatitis (NASH). We summarize the current research trend in lncRNAs and their [...] Read more.

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Open AccessFeature PaperReview

Changes in Non-Coding RNA in Depression and Bipolar Disorder: Can They Be Used as Diagnostic or Theranostic Biomarkers?

Andrew Gibbons

Suresh Sundram

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Brian Dean

Non-Coding RNA 2020, 6(3), 33; https://doi.org/10.3390/ncrna6030033 - 24 Aug 2020

Cited by 3 | Viewed by 2936

Abstract

The similarities between the depressive symptoms of Major Depressive Disorders (MDD) and Bipolar Disorders (BD) suggest these disorders have some commonality in their molecular pathophysiologies, which is not apparent from the risk genes shared between MDD and BD. This is significant, given the growing literature suggesting that changes in non-coding RNA may be important in both MDD and BD, because they are causing dysfunctions in the control of biochemical pathways that are affected in both disorders. Therefore, understanding the changes in non-coding RNA in MDD and BD will lead to a better understanding of how and why these disorders develop. Furthermore, as a significant number of individuals suffering with MDD and BD do not respond to medication, identifying non-coding RNA that are altered by the drugs used to treat these disorders offer the potential to identify biomarkers that could predict medication response. Such biomarkers offer the potential to quickly identify patients who are unlikely to respond to traditional medications so clinicians can refocus treatment strategies to ensure more effective outcomes for the patient. This review will focus on the evidence supporting the involvement of non-coding RNA in MDD and BD and their potential use as biomarkers for treatment response. Full article

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Open AccessArticle

Comparison of Poly-A⁺ Selection and rRNA Depletion in Detection of lncRNA in Two Equine Tissues Using RNA-seq

Theodore S. Kalbfleisch

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Non-Coding RNA 2020, 6(3), 32; https://doi.org/10.3390/ncrna6030032 - 21 Aug 2020

Cited by 4 | Viewed by 2828

Abstract

Long non-coding RNAs (lncRNAs) are untranslated regulatory transcripts longer than 200 nucleotides that can play a role in transcriptional, post-translational, and epigenetic regulation. Traditionally, RNA-sequencing (RNA-seq) libraries have been created by isolating transcriptomic RNA via poly-A⁺ selection. In the past 10 years, methods to perform ribosomal RNA (rRNA) depletion of total RNA have been developed as an alternative, aiming for better coverage of whole transcriptomic RNA, both polyadenylated and non-polyadenylated transcripts. The purpose of this study was to determine which library preparation method is optimal for lncRNA investigations in the horse. Using liver and cerebral parietal lobe tissues from two healthy Thoroughbred mares, RNA-seq libraries were prepared using standard poly-A⁺ selection and rRNA-depletion methods. Averaging the two biologic replicates, poly-A⁺ selection yielded 327 and 773 more unique lncRNA transcripts for liver and parietal lobe, respectively. More lncRNA were found to be unique to poly-A⁺ selected libraries, and rRNA-depletion identified small nucleolar RNA (snoRNA) to have a higher relative expression than in the poly-A⁺ selected libraries. Overall, poly-A⁺ selection provides a more thorough identification of total lncRNA in equine tissues while rRNA-depletion may allow for easier detection of snoRNAs. Full article

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Open AccessFeature PaperReview

Emerging Insights on the Biological Impact of Extracellular Vesicle-Associated ncRNAs in Multiple Myeloma

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Non-Coding RNA 2020, 6(3), 30; https://doi.org/10.3390/ncrna6030030 - 05 Aug 2020

Cited by 5 | Viewed by 3185

Abstract

Increasing evidence indicates that extracellular vesicles (EVs) released from both tumor cells and the cells of the bone marrow microenvironment contribute to the pathobiology of multiple myeloma (MM). Recent studies on the mechanisms by which EVs exert their biological activity have indicated that the non-coding RNA (ncRNA) cargo is key in mediating their effect on MM development and progression. In this review, we will first discuss the role of EV-associated ncRNAs in different aspects of MM pathobiology, including proliferation, angiogenesis, bone disease development, and drug resistance. Finally, since ncRNAs carried by MM vesicles have also emerged as a promising tool for early diagnosis and therapy response prediction, we will report evidence of their potential use as clinical biomarkers. Full article

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Open AccessReview

Macrophage Long Non-Coding RNAs in Pathogenesis of Cardiovascular Disease

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Non-Coding RNA 2020, 6(3), 28; https://doi.org/10.3390/ncrna6030028 - 11 Jul 2020

Cited by 3 | Viewed by 3109

Abstract

Chronic inflammation is inextricably linked to cardiovascular disease (CVD). Macrophages themselves play important roles in atherosclerosis, as well as acute and chronic heart failure. Although the role of macrophages in CVD pathophysiology is well-recognized, little is known regarding the precise mechanisms influencing their function in these contexts. Long non-coding RNAs (lncRNAs) have emerged as significant regulators of macrophage function; as such, there is rising interest in understanding how these nucleic acids influence macrophage signaling, cell fate decisions, and activity in health and disease. In this review, we summarize current knowledge regarding lncRNAs in directing various aspects of macrophage function in CVD. These include foam cell formation, Toll-like receptor (TLR) and NF-kβ signaling, and macrophage phenotype switching. This review will provide a comprehensive understanding concerning previous, ongoing, and future studies of lncRNAs in macrophage functions and their importance in CVD. Full article

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Open AccessReview

Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer

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Non-Coding RNA 2020, 6(3), 27; https://doi.org/10.3390/ncrna6030027 - 06 Jul 2020

Cited by 16 | Viewed by 4165

Abstract

Hypoxia is dangerous for oxygen-dependent cells, therefore, physiological adaption to cellular hypoxic conditions is essential. The transcription factor hypoxia-inducible factor (HIF) is the main regulator of hypoxic metabolic adaption reducing oxygen consumption and is regulated by gradual von Hippel-Lindau (VHL)-dependent proteasomal degradation. Beyond physiology, hypoxia is frequently encountered within solid tumors and first drugs are in clinical trials to tackle this pathway in cancer. Besides hypoxia, cancer cells may promote HIF expression under normoxic conditions by altering various upstream regulators, cumulating in HIF upregulation and enhanced glycolysis and angiogenesis, altogether promoting tumor proliferation and progression. Therefore, understanding the underlying molecular mechanisms is crucial to discover potential future therapeutic targets to evolve cancer therapy. Long non-coding RNAs (lncRNA) are a class of non-protein coding RNA molecules with a length of over 200 nucleotides. They participate in cancer development and progression and might act as either oncogenic or tumor suppressive factors. Additionally, a growing body of evidence supports the role of lncRNAs in the hypoxic and normoxic regulation of HIF and its subunits HIF-1α and HIF-2α in cancer. This review provides a comprehensive update and overview of lncRNAs as regulators of HIFs expression and activation and discusses and highlights potential involved pathways. Full article

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Open AccessFeature PaperReview

LncRNA NEAT1 in Paraspeckles: A Structural Scaffold for Cellular DNA Damage Response Systems?

Pierfrancesco Tassone

Nicola Amodio

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Antonino Neri

Non-Coding RNA 2020, 6(3), 26; https://doi.org/10.3390/ncrna6030026 - 01 Jul 2020

Cited by 14 | Viewed by 4572

Abstract

Nuclear paraspeckle assembly transcript 1 (NEAT1) is a long non-coding RNA (lncRNA) reported to be frequently deregulated in various types of cancers and neurodegenerative processes. NEAT1 is an indispensable structural component of paraspeckles (PSs), which are dynamic and membraneless nuclear bodies that affect different cellular functions, including stress response. Furthermore, increasing evidence supports the crucial role of NEAT1 and essential structural proteins of PSs (PSPs) in the regulation of the DNA damage repair (DDR) system. This review aims to provide an overview of the current knowledge on the involvement of NEAT1 and PSPs in DDR, which might strengthen the rationale underlying future NEAT1-based therapeutic options in tumor and neurodegenerative diseases. Full article

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Open AccessFeature PaperReview

LncRNAs in Non-Small-Cell Lung Cancer

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Non-Coding RNA 2020, 6(3), 25; https://doi.org/10.3390/ncrna6030025 - 30 Jun 2020

Cited by 30 | Viewed by 3512

Abstract

Lung cancer is associated with a high mortality, with around 1.8 million deaths worldwide in 2018. Non-small-cell lung cancer (NSCLC) accounts for around 85% of cases and, despite improvement in the management of NSCLC, most patients are diagnosed at advanced stage and the five-year survival remains around 15%. This highlights a need to identify novel ways to treat the disease to reduce the burden of NSCLC. Long non-coding RNAs (lncRNAs) are non-coding RNA molecules longer than 200 nucleotides in length which play important roles in gene expression and signaling pathways. Recently, lncRNAs were implicated in cancer, where their expression is dysregulated resulting in aberrant functions. LncRNAs were shown to function as both tumor suppressors and oncogenes in a variety of cancer types. Although there are a few well characterized lncRNAs in NSCLC, many lncRNAs remain un-characterized and their mechanisms of action largely unknown. LncRNAs have success as therapies in neurodegenerative diseases, and having a detailed understanding of their function in NSCLC may guide novel therapeutic approaches and strategies. This review discusses the role of lncRNAs in NSCLC tumorigenesis, highlighting their mechanisms of action and their clinical potential. Full article

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Open AccessReview

The Roles of Long Noncoding RNAs HNF1α-AS1 and HNF4α-AS1 in Drug Metabolism and Human Diseases

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Non-Coding RNA 2020, 6(2), 24; https://doi.org/10.3390/ncrna6020024 - 24 Jun 2020

Cited by 9 | Viewed by 2955

Abstract

Long noncoding RNAs (lncRNAs) are RNAs with a length of over 200 nucleotides that do not have protein-coding abilities. Recent studies suggest that lncRNAs are highly involved in physiological functions and diseases. lncRNAs HNF1α-AS1 and HNF4α-AS1 are transcripts of lncRNA genes HNF1α-AS1 and HNF4α-AS1, which are antisense lncRNA genes located in the neighborhood regions of the transcription factor (TF) genes HNF1α and HNF4α, respectively. HNF1α-AS1 and HNF4α-AS1 have been reported to be involved in several important functions in human physiological activities and diseases. In the liver, HNF1α-AS1 and HNF4α-AS1 regulate the expression and function of several drug-metabolizing cytochrome P450 (P450) enzymes, which also further impact P450-mediated drug metabolism and drug toxicity. In addition, HNF1α-AS1 and HNF4α-AS1 also play important roles in the tumorigenesis, progression, invasion, and treatment outcome of several cancers. Through interacting with different molecules, including miRNAs and proteins, HNF1α-AS1 and HNF4α-AS1 can regulate their target genes in several different mechanisms including miRNA sponge, decoy, or scaffold. The purpose of the current review is to summarize the identified functions and mechanisms of HNF1α-AS1 and HNF4α-AS1 and to discuss the future directions of research of these two lncRNAs. Full article

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Open AccessArticle

Dynamic Expression of Long Non-Coding RNAs Throughout Parasite Sexual and Neural Maturation in Schistosoma Japonicum

Lucas F. Maciel

David A. Morales-Vicente

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Sergio Verjovski-Almeida

Non-Coding RNA 2020, 6(2), 15; https://doi.org/10.3390/ncrna6020015 - 01 Apr 2020

Cited by 4 | Viewed by 2865

Abstract

Schistosoma japonicum is a flatworm that causes schistosomiasis, a neglected tropical disease. S. japonicum RNA-Seq analyses has been previously reported in the literature on females and males obtained during sexual maturation from 14 to 28 days post-infection in mouse, resulting in the identification of protein-coding genes and pathways, whose expression levels were related to sexual development. However, this work did not include an analysis of long non-coding RNAs (lncRNAs). Here, we applied a pipeline to identify and annotate lncRNAs in 66 S. japonicum RNA-Seq publicly available libraries, from different life-cycle stages. We also performed co-expression analyses to find stage-specific lncRNAs possibly related to sexual maturation. We identified 12,291 S. japonicum expressed lncRNAs. Sequence similarity search and synteny conservation indicated that some 14% of S. japonicum intergenic lncRNAs have synteny conservation with S. mansoni intergenic lncRNAs. Co-expression analyses showed that lncRNAs and protein-coding genes in S. japonicum males and females have a dynamic co-expression throughout sexual maturation, showing differential expression between the sexes; the protein-coding genes were related to the nervous system development, lipid and drug metabolism, and overall parasite survival. Co-expression pattern suggests that lncRNAs possibly regulate these processes or are regulated by the same activation program as that of protein-coding genes. Full article

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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Pre-therapeutic efficacy of miR-124 in medulloblastoma
Authors: Buzzetti Marta, Morlando Sonia, Di Leva Gianpiero.
Affiliation: School of Pharmacy and Bioengineering, Guy Hilton Research Facility, Keele University, Keele, Staffordshire ST5 5BG, UK

Title: Non coding RNAs: strategy for viruses offensive?
Authors: Alessia Gallo
Affiliation: Unit of Regenerative Medicine and Biomedical Technologies IRCCS-ISMETT (Mediterranean Institute for Transplantation and Advanced Specialized Therapies) Via Tricomi, 5 Palermo 90127

Title: Non-coding RNAs in retinoic acid-driven cell differentiation and disease
Authors: Diego Franco Jaime
Affiliation: Universidad de Jaén, Departamento de Biología Experimental, B3-362

Title: Circulating RNAs associated with the metabolic syndrome
Authors: Louise Torp Dalgaard
Affiliation: Eukaryot Cellebiologi, The Department of Science, Systems and Models, Roskilde University, Universitetsvej 1, 18.2, DK-4000, Roskilde, Denmark

Title: ncRNAs in liquid biopsy
Authors: Peter Gahan；; Heidi Schwarzenbach
Affiliation: Fondazione “Enrico Puccinelli” Onlus, Perugia, Italy

Title: Bioinformatic analyses of conserved microRNAs-target gene networks between the human left ventricle and peripheral plasma could reveal new functional biomarkers of ischaemic heart disease in diabetic patients
Authors: Maryam Anwar1, Junyi Liu1, Ibrahim Nasser1, Gianni Angelini1,2, Prakash Punjabi1, Kerrie Ford, Aranzazu Chamorro-Jorganes1, Costanza Emanueli1, 2
Affiliation: 1National Heart and Lung Institute, Imperial College London, London, UK 2Bristol Heart Institute, University of Bristol, Bristol, UK

Title: microRNAs in the 8q24 region and risk of cancer
Authors: Barbara Pardini
Affiliation: Italian Institute for Genomic Medicine - IIGM, c/o FPO IRCCS, 10060 Candiolo (To), Italy

Title: Beyond base pairing: complex interactions between structured noncoding RNAs
Authors: Jinwei Zhang
Affiliation: Laboratory of Molecular Biology NIDDK, NIH 50 South Drive, Room 4503 Bethesda, MD 20892

Title: non coding RNA impacting on mitochondrial functions
Authors: Nicola Amodio
Affiliation: Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro, 88100 Catanzaro, Italy

Title: Evolution of the boundary between coding and noncoding RNA
Authors: Yusuke Suenaga
Affiliation: Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba, Japan

Title: Bottleneck Spatio-Temporal Attention Network for RNA sequences classification of coding or non-coding transcripts
Authors: Yusuke Suenaga
Affiliation: Department of Molecular Carcinogenesis, Chiba Cancer Center Research Institute, 666-2 Nitona, Chuoh-ku, Chiba, Japan

Title: Direct Comparison of Chol-siRNA and Chol-DsiRNA Polyplexes Targeting STAT3 in a Syngeneic Murine Model of TNBC
Authors: Zhen Ye2, Mai Mohamed Abdelmoaty2,3, Stephen M. Curran2, Shetty Ravi Dyavar4, Devendra Kumar2, Yazen Alnouti2, Don W. Coulter6, Rakesh K. Singh1,5, Joseph A. Vetro1,2,*
Affiliation: 1Center for Drug Delivery and Nanomedicine and 2Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198-6025, USA 3Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt 4Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198-6025, USA 5Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198-5900, USA. 6Department of Pediatrics, Division of Pediatric Hematology/Oncology, Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE 68198-2168, USA

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