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LncRNAs in Health and Disease
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LncRNAs in Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 30070

Special Issue Editor

Prof. Dr. Francesco Crea

E-Mail Website
Guest Editor
Senior Lecturer and Research Director, Department of Life, Health and Chemical Sciences, Open University, Milton Keynes, UK
Interests: cancer; epigenetics; ncRNAs; cancer modeling
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Long non-coding RNAs (LncRNAs) are a recently discovered type of RNA that plays relevant roles in physiology. Mammalian cells can produce thousands of LncRNAs that regulate gene expression via multiple mechanisms, including direct interaction with proteins, mRNAs, and miRNAs.

In physiology, LncRNAs have been shown to modulate basic functions such as alternative splicing or epigenetic modification of gene expression to perform pivotal roles in cell specification, development, and immunity. Interestingly, LncRNAs expression and function are de-regulated in several pathological conditions including cancer, cardiovascular diseases, and inflammation. Due to their contribution to the pathophysiology of various human diseases and their tissue-specific expression, LncRNAs have attracted attention as therapeutic targets and biomarkers.

Given the rapidly-evolving discovery rate of new roles of LncRNAs in health and disease, there is a current demand for a constant updating of the knowledge in this field. This Special Issue welcomes original research articles and review manuscripts in the fields of lncRNA physiology and pathology. These contributions will document new advances in the field of LncRNAs with special emphasis on novel therapeutic and diagnostic approaches for LncRNA-driven diseases.

Dr. Francesco Crea
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 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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • epigenetics
  • gene expression regulation

Published Papers (7 papers)

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Research

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13 pages, 1981 KiB  
Article
The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation
by David Roig-Carles, Holly Jackson, Katie F. Loveson, Alan Mackay, Rebecca L. Mather, Ella Waters, Massimiliano Manzo, Ilaria Alborelli, Jon Golding, Chris Jones, Helen L. Fillmore and Francesco Crea
Int. J. Mol. Sci. 2021, 22(17), 9165; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22179165 - 25 Aug 2021
Cited by 5 | Viewed by 3013
Abstract
Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in [...] Read more.
Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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18 pages, 5417 KiB  
Article
Characterization of Long Non-Coding RNAs in Systemic Sclerosis Monocytes: A Potential Role for PSMB8-AS1 in Altered Cytokine Secretion
by Nila H. Servaas, Barbara Mariotti, Maarten van der Kroef, Catharina G. K. Wichers, Aridaman Pandit, Flavia Bazzoni, Timothy R. D. J. Radstake and Marzia Rossato
Int. J. Mol. Sci. 2021, 22(9), 4365; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094365 - 22 Apr 2021
Cited by 11 | Viewed by 2548
Abstract
Systemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demonstrated that the dysregulation of [...] Read more.
Systemic sclerosis (SSc) is a chronic autoimmune disease mainly affecting the connective tissue. In SSc patients, monocytes are increased in circulation, infiltrate affected tissues, and show a pro-inflammatory activation status, including the so-called interferon (IFN) signature. We previously demonstrated that the dysregulation of the IFN response in SSc monocytes is sustained by altered epigenetic factors as well as by upregulation of the long non-coding RNA (lncRNA) NRIR. Considering the enormously diverse molecular functions of lncRNAs in immune regulation, the present study investigated the genome-wide profile of lncRNAs in SSc monocytes, with the aim to further unravel their possible role in monocyte dysregulation and disease pathogenesis. Transcriptomic data from two independent cohorts of SSc patients identified 886 lncRNAs with an altered expression in SSc monocytes. Differentially expressed lncRNAs were correlated with neighboring protein coding genes implicated in the regulation of IFN responses and apoptotic signaling in SSc monocytes. In parallel, gene co-expression network analysis identified the lncRNA PSMB8-AS1 as a top-ranking hub gene in co-expression modules implicated in cell activation and response to viral and external stimuli. Functional characterization of PSMB8-AS1 in monocytes demonstrated that this lncRNA is involved in the secretion of IL-6 and TNFα, two pivotal pro-inflammatory cytokines altered in the circulation of SSc patients and associated with fibrosis and disease severity. Collectively, our data showed that lncRNAs are linked to monocyte dysregulation in SSc, and highlight their potential contribution to disease pathogenesis. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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17 pages, 7461 KiB  
Article
Identification of the 3-lncRNA Signature as a Prognostic Biomarker for Colorectal Cancer
by Shuzhen Liu, Qing Cao, Guoyan An, Bianbian Yan and Lei Lei
Int. J. Mol. Sci. 2020, 21(24), 9359; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249359 - 08 Dec 2020
Cited by 46 | Viewed by 3290
Abstract
Colorectal cancer (CRC) is one of the most common malignant carcinomas in the world, and metastasis is the main cause of CRC-related death. However, the molecular network involved in CRC metastasis remains poorly understood. Long noncoding RNA (lncRNA) plays a vital role in [...] Read more.
Colorectal cancer (CRC) is one of the most common malignant carcinomas in the world, and metastasis is the main cause of CRC-related death. However, the molecular network involved in CRC metastasis remains poorly understood. Long noncoding RNA (lncRNA) plays a vital role in tumorigenesis and may act as a competing endogenous RNA (ceRNA) to affect the expression of mRNA by suppressing miRNA function. In this study, we identified 628 mRNAs, 144 lncRNAs, and 25 miRNAs that are differentially expressed (DE) in metastatic CRC patients compared with nonmetastatic CRC patients from the Cancer Genome Atlas (TCGA) database. Functional enrichment analyses confirmed that the identified DE mRNAs are extensively involved in CRC tumorigenesis and migration. By bioinformatics analysis, we constructed a metastasis-associated ceRNA network for CRC that includes 28 mRNAs, 12 lncRNAs, and 15 miRNAs. We then performed multivariate Cox regression analysis on the ceRNA-related DE lncRNAs and identified a 3-lncRNA signature (LINC00114, LINC00261, and HOTAIR) with the greatest prognostic value for CRC. Clinical feature analysis and functional enrichment analysis further proved that these three lncRNAs are involved in CRC tumorigenesis. Finally, we used Transwell, Cell Counting Kit (CCK)-8, and colony formation assays to clarify that the inhibition of LINC00114 promotes the migratory, invasive, and proliferative abilities of CRC cells. The results of the luciferase assay suggest that LINC00114 is the direct target of miR-135a, which also verified the ceRNA network. In summary, this study provides a metastasis-associated ceRNA network for CRC and suggests that the 3-lncRNA signature may be a useful candidate for the diagnosis and prognosis of CRC. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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Review

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33 pages, 1997 KiB  
Review
Long Non-Coding RNAs as Functional Codes for Oral Cancer: Translational Potential, Progress and Promises
by Cing-Syuan Lei, Hsing-Jien Kung and Jing-Wen Shih
Int. J. Mol. Sci. 2021, 22(9), 4903; https://doi.org/10.3390/ijms22094903 - 05 May 2021
Cited by 9 | Viewed by 2555
Abstract
Oral cancer is one of the leading malignant tumors worldwide. Despite the advent of multidisciplinary approaches, the overall prognosis of patients with oral cancer is poor, mainly due to late diagnosis. There is an urgent need to develop valid biomarkers for early detection [...] Read more.
Oral cancer is one of the leading malignant tumors worldwide. Despite the advent of multidisciplinary approaches, the overall prognosis of patients with oral cancer is poor, mainly due to late diagnosis. There is an urgent need to develop valid biomarkers for early detection and effective therapies. Long non-coding RNAs (lncRNAs) are recognized as key elements of gene regulation, with pivotal roles in various physiological and pathological processes, including cancer. Over the past few years, an exponentially growing number of lncRNAs have been identified and linked to tumorigenesis and prognosis outcomes in oral cancer, illustrating their emerging roles in oral cancer progression and the associated signaling pathways. Herein, we aim to summarize the most recent advances made concerning oral cancer-associated lncRNA, and their expression, involvement, and potential clinical impact, reported to date, with a specific focus on the lncRNA-mediated molecular regulation in oncogenic signaling cascades and oral malignant progression, while exploring their potential, and challenges, for clinical applications as biomarkers or therapeutic targets for oral cancer. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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20 pages, 841 KiB  
Review
Roles and Mechanisms of the Long Noncoding RNAs in Cervical Cancer
by Miguel Ángel Cáceres-Durán, Ândrea Ribeiro-dos-Santos and Amanda Ferreira Vidal
Int. J. Mol. Sci. 2020, 21(24), 9742; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249742 - 21 Dec 2020
Cited by 30 | Viewed by 6281
Abstract
Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are [...] Read more.
Cervical cancer (CC) continues to be one of the leading causes of death for women across the world. Although it has been determined that papillomavirus infection is one of the main causes of the etiology of the disease, genetic and epigenetic factors are also required for its progression. Among the epigenetic factors are included the long noncoding RNAs (lncRNAs), transcripts of more than 200 nucleotides (nt) that generally do not code for proteins and have been associated with diverse functions such as the regulation of transcription, translation, RNA metabolism, as well as stem cell maintenance and differentiation, cell autophagy and apoptosis. Recently, studies have begun to characterize the aberrant regulation of lncRNAs in CC cells and tissues, including Homeobox transcript antisense RNA (HOTAIR), H19, Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), Cervical Carcinoma High-Expressed 1 (CCHE1), Antisense noncoding RNA in the inhibitors of cyclin-dependent kinase 4 (ANRIL), Growth arrest special 5 (GAS5) and Plasmacytoma variant translocation 1 (PVT1). They have been associated with several disease-related processes such as cell growth, cell proliferation, cell survival, metastasis and invasion as well as therapeutic resistance, and are novel potential biomarkers for diagnosis and prognosis in CC. In this review, we summarize the current literature regarding the knowledge we have about the roles and mechanisms of the lncRNAs in cervical neoplasia. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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16 pages, 2168 KiB  
Review
Long Non-Coding RNA Associated with Cholesterol Homeostasis and Its Involvement in Metabolic Diseases
by Kang-Hoon Lee, Hyeon-Ji Hwang and Je-Yoel Cho
Int. J. Mol. Sci. 2020, 21(21), 8337; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218337 - 06 Nov 2020
Cited by 10 | Viewed by 2354
Abstract
Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has [...] Read more.
Cholesterol is an essential cell component that functions to create and maintain all kinds of cell membranes and lipoprotein particles. It is crucial to maintain the proper amount of cholesterol at both the cellular and systemic level. Recently, the importance of cholesterol has been reported not only in various cell development processes but also in the development of diseases. Furthermore, the involvement of long non-coding RNAs (lncRNAs), which are regarded as important epigenetic regulators in gene expression, has also been reported in cholesterol homeostasis. It is thus necessary to summarize the research on lncRNAs related to cholesterol with increased interest. This review organized the role of lncRNAs according to the major issues in cholesterol homeostasis: efflux, metabolism and synthesis, and disease process. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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20 pages, 440 KiB  
Review
Biomarkers in Colorectal Cancer: Current Research and Future Prospects
by Olorunseun O. Ogunwobi, Fahad Mahmood and Akinfemi Akingboye
Int. J. Mol. Sci. 2020, 21(15), 5311; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155311 - 27 Jul 2020
Cited by 124 | Viewed by 9098
Abstract
Colorectal cancer (CRC) is a leading cause of death worldwide, despite progress made in detection and management through surgery, chemotherapy, radiotherapy, and immunotherapy. Novel therapeutic agents have improved survival in both the adjuvant and advanced disease settings, albeit with an increased risk of [...] Read more.
Colorectal cancer (CRC) is a leading cause of death worldwide, despite progress made in detection and management through surgery, chemotherapy, radiotherapy, and immunotherapy. Novel therapeutic agents have improved survival in both the adjuvant and advanced disease settings, albeit with an increased risk of toxicity and cost. However, metastatic disease continues to have a poor long-term prognosis and significant challenges remain due to late stage diagnosis and treatment failure. Biomarkers are a key tool in early detection, prognostication, survival, and predicting treatment response. The past three decades have seen advances in genomics and molecular pathology of cancer biomarkers, allowing for greater individualization of therapy with a positive impact on survival outcomes. Clinically useful predictive biomarkers aid clinical decision making, such as the presence of KRAS gene mutations predicting benefit from epidermal growth factor receptor (EGFR) inhibiting antibodies. However, few biomarkers have been translated into clinical practice highlighting the need for further investigation. We review a range of protein, DNA and RNA-based biomarkers under investigation for diagnostic, predictive, and prognostic properties for CRC. In particular, long non-coding RNAs (lncRNA), have been investigated as biomarkers in a range of cancers including colorectal cancer. Specifically, we evaluate the potential role of lncRNA plasmacytoma variant translocation 1 (PVT1), an oncogene, as a diagnostic, prognostic, and therapeutic biomarker in colorectal cancer. Full article
(This article belongs to the Special Issue LncRNAs in Health and Disease)
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