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ncRNA
Volume 9
Issue 4
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Non-Coding RNA, Volume 9, Issue 4 (August 2023) – 12 articles

Cover Story (view full-size image): Doxorubicin causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. We hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. We analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. We treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB. View this paper
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15 pages, 1969 KiB  
Article
Investigation into the Role of Long-Non-Coding RNA MIAT in Leukemia
by Alessia Ostini and Mirna Mourtada-Maarabouni
Non-Coding RNA 2023, 9(4), 47; https://doi.org/10.3390/ncrna9040047 - 11 Aug 2023
Viewed by 2023
Abstract
Myocardial Infarction Associated Transcript (MIAT) is a nuclear long non-coding RNA (LncRNA) with four different splicing variants. MIAT dysregulation is associated with carcinogenesis, mainly acting as an oncogene regulating cellular growth, invasion, and metastasis. The aim of the current study is [...] Read more.
Myocardial Infarction Associated Transcript (MIAT) is a nuclear long non-coding RNA (LncRNA) with four different splicing variants. MIAT dysregulation is associated with carcinogenesis, mainly acting as an oncogene regulating cellular growth, invasion, and metastasis. The aim of the current study is to investigate the role of MIAT in the regulation of T and chronic myeloid leukemic cell survival. To this end, MIAT was silenced using MIAT-specific siRNAs in leukemic cell lines, and functional assays were performed thereafter. This investigation also aims to investigate the effects of MIAT silencing on the expression of core genes involved in cancer. Functional studies and gene expression determination confirm that MIAT knockdown not only affects short- and long-term survival and the apoptosis of leukemic cells but also plays a pivotal role in the alteration of key genes involved in cancer, including c-MYC and HIF-1A. Our observations suggest that MIAT could act as an oncogene and it has the potential to be used not only as a reliable biomarker for leukemia, but also be employed for prognostic and therapeutic purposes. Full article
(This article belongs to the Special Issue Current Strategies to Investigate the Role of ncRNAs in Carcinogenesis)
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3 pages, 165 KiB  
Editorial
Methods and Tools in RNA Biology
by Mirolyuba Ilieva and Shizuka Uchida
Non-Coding RNA 2023, 9(4), 46; https://doi.org/10.3390/ncrna9040046 - 10 Aug 2023
Viewed by 1243
Abstract
Breakthroughs in innovative techniques and instruments have driven the exploration of non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) [...] Full article
(This article belongs to the Special Issue Methods and Tools in RNA Biology)
14 pages, 1790 KiB  
Communication
Structural Modifications and Novel Protein-Binding Sites in Pre-miR-675—Explaining Its Regulatory Mechanism in Carcinogenesis
by Abhishek Dey
Non-Coding RNA 2023, 9(4), 45; https://doi.org/10.3390/ncrna9040045 - 10 Aug 2023
Viewed by 2199
Abstract
Pre-miR-675 is a microRNA expressed from the exon 1 of H19 long noncoding RNA, and the atypical expression of pre-miR-675 has been linked with several diseases and disorders including cancer. To execute its function inside the cell, pre-miR-675 is folded into a particular [...] Read more.
Pre-miR-675 is a microRNA expressed from the exon 1 of H19 long noncoding RNA, and the atypical expression of pre-miR-675 has been linked with several diseases and disorders including cancer. To execute its function inside the cell, pre-miR-675 is folded into a particular conformation, which aids in its interaction with several other biological molecules. However, the exact folding dynamics of pre-miR-675 and its protein-binding motifs are currently unknown. Moreover, how H19 lncRNA and pre-miR-675 crosstalk and modulate each other’s activities is also unclear. The detailed structural analysis of pre-miR-675 in this study determines its earlier unknown conformation and identifies novel protein-binding sites on pre-miR-675, thus making it an excellent therapeutic target against cancer. Co-folding analysis between H19 lncRNA and pre-miR-675 determine structural transformations in pre-miR-675, thus describing the earlier unknown mechanism of interaction between these two molecules. Comprehensively, this study details the conformation of pre-miR-675 and its protein-binding sites and explains its relationship with H19 lncRNA, which can be interpreted to understand the role of pre-miR-675 in the development and progression of tumorigenesis and designing new therapeutics against cancers. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Clinical Implications of Non-coding RNAs in Cancer)
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21 pages, 3821 KiB  
Review
Long Non-Coding RNA Signatures in Lymphopoiesis and Lymphoid Malignancies
by Hamed Baghdadi, Reza Heidari, Mahdi Zavvar, Nazanin Ahmadi, Mehdi Shakouri Khomartash, Mahmoud Vahidi, Mojgan Mohammadimehr, Davood Bashash and Mahdi Ghorbani
Non-Coding RNA 2023, 9(4), 44; https://doi.org/10.3390/ncrna9040044 - 01 Aug 2023
Cited by 1 | Viewed by 1650
Abstract
Lymphoid cells play a critical role in the immune system, which includes three subgroups of T, B, and NK cells. Recognition of the complexity of the human genetics transcriptome in lymphopoiesis has revolutionized our understanding of the regulatory potential of RNA in normal [...] Read more.
Lymphoid cells play a critical role in the immune system, which includes three subgroups of T, B, and NK cells. Recognition of the complexity of the human genetics transcriptome in lymphopoiesis has revolutionized our understanding of the regulatory potential of RNA in normal lymphopoiesis and lymphoid malignancies. Long non-coding RNAs (lncRNAs) are a class of RNA molecules greater than 200 nucleotides in length. LncRNAs have recently attracted much attention due to their critical roles in various biological processes, including gene regulation, chromatin organization, and cell cycle control. LncRNAs can also be used for cell differentiation and cell fate, as their expression patterns are often specific to particular cell types or developmental stages. Additionally, lncRNAs have been implicated in lymphoid differentiation, such as regulating T-cell and B-cell development, and their expression has been linked to immune-associated diseases such as leukemia and lymphoma. In addition, lncRNAs have been investigated as potential biomarkers for diagnosis, prognosis, and therapeutic response to disease management. In this review, we provide an overview of the current knowledge about the regulatory role of lncRNAs in physiopathology processes during normal lymphopoiesis and lymphoid leukemia. Full article
(This article belongs to the Special Issue Non-Coding RNA in the Immune System)
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13 pages, 1407 KiB  
Article
Effects of Controlled Ozone Exposure on Circulating microRNAs and Vascular and Coagulation Biomarkers: A Mediation Analysis
by Hao Chen, Syed Masood, Ana G. Rappold, David Diaz-Sanchez, James M. Samet and Haiyan Tong
Non-Coding RNA 2023, 9(4), 43; https://doi.org/10.3390/ncrna9040043 - 01 Aug 2023
Viewed by 1183
Abstract
Exposure to ozone (O3) is associated with adverse respiratory and cardiovascular outcomes. Alterations in circulating microRNAs (miRNAs) may contribute to the adverse vascular effects of O3 exposure through inter-cellular communication resulting in post-transcriptional regulation of messenger RNAs by miRNAs. In [...] Read more.
Exposure to ozone (O3) is associated with adverse respiratory and cardiovascular outcomes. Alterations in circulating microRNAs (miRNAs) may contribute to the adverse vascular effects of O3 exposure through inter-cellular communication resulting in post-transcriptional regulation of messenger RNAs by miRNAs. In this study, we investigated whether O3 exposure induces alterations in circulating miRNAs that can mediate effects on downstream vascular and coagulation biomarkers. Twenty-three healthy male adults were exposed on successive days to filtered air and 300 ppb O3 for 2 h. Circulating miRNA and protein biomarkers were quantified after each exposure session. The data were subjected to mixed-effects model and mediation analyses for the statistical analyses. The results showed that the expression level of multiple circulating miRNAs (e.g., miR-19a-3p, miR-34a-5p) was significantly associated with O3 exposure. Pathway analysis showed that these miRNAs were predictive of changing levels of downstream biomarkers [e.g., D-dimer, C-reactive protein, tumor necrosis factor α (TNFα)]. Mediation analysis showed that miR-19a-3p may be a significant mediator of O3-exposure-induced changes in blood TNFα levels [0.08 (0.01, 0.15), p = 0.02]. In conclusion, this preliminary study showed that O3 exposure of healthy male adults resulted in changes in circulating miRNAs, some of which may mediate vascular effects of O3 exposure. Full article
(This article belongs to the Special Issue Non-coding RNA in the USA: Latest Advances and Perspectives)
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23 pages, 41554 KiB  
Review
Crosstalk between Long Non-Coding RNA and Spliceosomal microRNA as a Novel Biomarker for Cancer
by Maram Arafat and Ruth Sperling
Non-Coding RNA 2023, 9(4), 42; https://doi.org/10.3390/ncrna9040042 - 31 Jul 2023
Cited by 2 | Viewed by 1622
Abstract
Non-coding RNAs (ncRNAs) play diverse roles in regulating cellular processes and have been implicated in pathological conditions, including cancer, where interactions between ncRNAs play a role. Relevant here are (i) microRNAs (miRNAs), mainly known as negative regulators of gene expression in the cytoplasm. [...] Read more.
Non-coding RNAs (ncRNAs) play diverse roles in regulating cellular processes and have been implicated in pathological conditions, including cancer, where interactions between ncRNAs play a role. Relevant here are (i) microRNAs (miRNAs), mainly known as negative regulators of gene expression in the cytoplasm. However, identification of miRNAs in the nucleus suggested novel nuclear functions, and (ii) long non-coding RNA (lncRNA) regulates gene expression at multiple levels. The recent findings of miRNA in supraspliceosomes of human breast and cervical cancer cells revealed new candidates of lncRNA targets. Here, we highlight potential cases of crosstalk between lncRNA and supraspliceosomal miRNA expressed from the same genomic region, having complementary sequences. Through RNA:RNA base pairing, changes in the level of one partner (either miRNA or lncRNA), as occur in cancer, could affect the level of the other, which might be involved in breast and cervical cancer. An example is spliceosomal mir-7704 as a negative regulator of the oncogenic lncRNA HAGLR. Because the expression of spliceosomal miRNA is cell-type-specific, the list of cis-interacting lncRNA:spliceosomal miRNA presented here is likely just the tip of the iceberg, and such interactions are likely relevant to additional cancers. We thus highlight the potential of lncRNA:spliceosomal miRNA interactions as novel targets for cancer diagnosis and therapies. Full article
(This article belongs to the Special Issue Recent Advances in Chemical Biology to Study and Target ncRNAs)
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15 pages, 1507 KiB  
Systematic Review
Conservation and Targets of miR-71: A Systematic Review and Meta-Analysis
by Devin Naidoo, Ryan Brennan and Alexandre de Lencastre
Non-Coding RNA 2023, 9(4), 41; https://doi.org/10.3390/ncrna9040041 - 26 Jul 2023
Viewed by 1458
Abstract
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles [...] Read more.
MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles in human disease. First identified as an aging-associated gene in C. elegans, miR-71, a miRNA, has a demonstrated capability of regulating processes in numerous different invertebrates, including platyhelminths, mollusks, and insects. In these organisms, miR-71 has been shown to affect a diverse range of pathways, including aging, development, and immune response. However, the exact mechanisms by which miR-71 regulates these pathways are not completely understood. In this paper, we review the identified functions of miR-71 across multiple organisms, including identified gene targets, pathways, and the conditions which affect regulatory action. Additionally, the degree of conservation of miR-71 in the evaluated organisms and the conservation of their predicted binding sites in target 3′ UTRs was measured. These studies may provide an insight on the patterns, interactions, and conditions in which miR-71 is able to exert genotypic and phenotypic influence. Full article
(This article belongs to the Special Issue ncRNAs to Target Molecular Pathways)
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4 pages, 1191 KiB  
Commentary
Phosphate Deficiency: A Tale from the End of PILNCR2
by Santosh Kumar Upadhyay
Non-Coding RNA 2023, 9(4), 40; https://doi.org/10.3390/ncrna9040040 - 25 Jul 2023
Viewed by 1909
Abstract
A deficiency in inorganic phosphate (Pi) induces the expression of miRNA399 and the accumulation of its target Pi transporters (PHT1s) mRNA, which is contrary to the goal of miRNA-mediated gene regulation. Recently, a novel mechanism of RNA/RNA-duplex formation between the transcripts [...] Read more.
A deficiency in inorganic phosphate (Pi) induces the expression of miRNA399 and the accumulation of its target Pi transporters (PHT1s) mRNA, which is contrary to the goal of miRNA-mediated gene regulation. Recently, a novel mechanism of RNA/RNA-duplex formation between the transcripts of a Pi deficiency-induced long non-coding RNA (PILNCR2) and PHT1s has been reported, which prevents the binding and cleavage of miRNA399 to PHT1 mRNAs, thereby providing tolerance of Pi-deficient conditions. Moreover, the way in which ribosomes move through the RNA/RNA-duplex for the translation of PHT1 transporter proteins remains elusive. Full article
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24 pages, 4590 KiB  
Article
DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes
by Rebecca Distefano, Mirolyuba Ilieva, Jens Hedelund Madsen, Sarah Rennie and Shizuka Uchida
Non-Coding RNA 2023, 9(4), 39; https://doi.org/10.3390/ncrna9040039 - 13 Jul 2023
Cited by 3 | Viewed by 1910
Abstract
Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called [...] Read more.
Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB. Full article
(This article belongs to the Special Issue Methods and Tools in RNA Biology)
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28 pages, 1490 KiB  
Review
Functions of Circular RNA in Human Diseases and Illnesses
by Alison Gu, Dabbu Kumar Jaijyan, Shaomin Yang, Mulan Zeng, Shaokai Pei and Hua Zhu
Non-Coding RNA 2023, 9(4), 38; https://doi.org/10.3390/ncrna9040038 - 04 Jul 2023
Cited by 9 | Viewed by 2954
Abstract
Circular RNAs (circRNAs) represent single-stranded RNA species that contain covalently closed 3′ and 5′ ends that provide them more stability than linear RNA, which has free ends. Emerging evidence indicates that circRNAs perform essential functions in many DNA viruses, including coronaviruses, Epstein–Barr viruses, [...] Read more.
Circular RNAs (circRNAs) represent single-stranded RNA species that contain covalently closed 3′ and 5′ ends that provide them more stability than linear RNA, which has free ends. Emerging evidence indicates that circRNAs perform essential functions in many DNA viruses, including coronaviruses, Epstein–Barr viruses, cytomegalovirus, and Kaposi sarcoma viruses. Recent studies have confirmed that circRNAs are present in viruses, including DNA and RNA viruses, and play various important functions such as evading host immune response, disease pathogenesis, protein translation, miRNA sponges, regulating cell proliferation, and virus replication. Studies have confirmed that circRNAs can be biological signatures or pathological markers for autoimmune diseases, neurological diseases, and cancers. However, our understanding of circRNAs in DNA and RNA viruses is still limited, and functional evaluation of viral and host circRNAs is essential to completely understand their biological functions. In the present review, we describe the metabolism and cellular roles of circRNA, including its roles in various diseases and viral and cellular circRNA functions. Circular RNAs are found to interact with RNA, proteins, and DNA, and thus can modulate cellular processes, including translation, transcription, splicing, and other functions. Circular RNAs interfere with various signaling pathways and take part in vital functions in various biological, physiological, cellular, and pathophysiological processes. We also summarize recent evidence demonstrating cellular and viral circRNA’s roles in DNA and RNA viruses in this growing field of research. Full article
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13 pages, 718 KiB  
Review
Impacts of MicroRNA-483 on Human Diseases
by Katy Matson, Aaron Macleod, Nirali Mehta, Ellie Sempek and Xiaoqing Tang
Non-Coding RNA 2023, 9(4), 37; https://doi.org/10.3390/ncrna9040037 - 28 Jun 2023
Cited by 4 | Viewed by 1712
Abstract
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression by targeting specific messenger RNAs (mRNAs) in distinct cell types. This review provides a com-prehensive overview of the current understanding regarding the involvement of miR-483-5p and miR-483-3p in various physiological and pathological [...] Read more.
MicroRNAs (miRNAs) are short non-coding RNA molecules that regulate gene expression by targeting specific messenger RNAs (mRNAs) in distinct cell types. This review provides a com-prehensive overview of the current understanding regarding the involvement of miR-483-5p and miR-483-3p in various physiological and pathological processes. Downregulation of miR-483-5p has been linked to numerous diseases, including type 2 diabetes, fatty liver disease, diabetic nephropathy, and neurological injury. Accumulating evidence indicates that miR-483-5p plays a crucial protective role in preserving cell function and viability by targeting specific transcripts. Notably, elevated levels of miR-483-5p in the bloodstream strongly correlate with metabolic risk factors and serve as promising diagnostic markers. Consequently, miR-483-5p represents an appealing biomarker for predicting the risk of developing diabetes and cardiovascular diseases and holds potential as a therapeutic target for intervention strategies. Conversely, miR-483-3p exhibits significant upregulation in diabetes and cardiovascular diseases and has been shown to induce cellular apoptosis and lipotoxicity across various cell types. However, some discrepancies regarding its precise function have been reported, underscoring the need for further investigation in this area. Full article
(This article belongs to the Special Issue Women’s Special Issue Series: Noncoding RNAs and Diseases)
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16 pages, 1223 KiB  
Review
LncRNA Functional Screening in Organismal Development
by Yang Li, Huicong Zhai, Lingxiu Tong, Cuicui Wang, Zhiming Xie and Ke Zheng
Non-Coding RNA 2023, 9(4), 36; https://doi.org/10.3390/ncrna9040036 - 28 Jun 2023
Viewed by 1409
Abstract
Controversy continues over the functional prevalence of long non-coding RNAs (lncRNAs) despite their being widely investigated in all kinds of cells and organisms. In animals, lncRNAs have aroused general interest from exponentially increasing transcriptomic repertoires reporting their highly tissue-specific and developmentally dynamic expression, [...] Read more.
Controversy continues over the functional prevalence of long non-coding RNAs (lncRNAs) despite their being widely investigated in all kinds of cells and organisms. In animals, lncRNAs have aroused general interest from exponentially increasing transcriptomic repertoires reporting their highly tissue-specific and developmentally dynamic expression, and more importantly, from growing experimental evidence supporting their functionality in facilitating organogenesis and individual fitness. In mammalian testes, while a great multitude of lncRNA species are identified, only a minority of them have been shown to be useful, and even fewer have been demonstrated as true requirements for male fertility using knockout models to date. This noticeable gap is attributed to the virtual existence of a large number of junk lncRNAs, the lack of an ideal germline culture system, difficulty in loss-of-function interrogation, and limited screening strategies. Facing these challenges, in this review, we discuss lncRNA functionality in organismal development and especially in mouse testis, with a focus on lncRNAs with functional screening. Full article
(This article belongs to the Special Issue Recent Advances in Chemical Biology to Study and Target ncRNAs)
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