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Cells
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lncRNA and Cancer
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lncRNA and Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 51512

Special Issue Editor

Dr. Kate Lawrenson

E-Mail Website1 Website2
Guest Editor
Women’s Cancer Program at the Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, USA
Interests: The Lawrenson lab explores the factors that drive the deregulation of ovarian cancer transcriptomes. We leverage this insight into gene regulation to understand how inherited and acquired genetic variants contribute to the development of ovarian cancer.

Special Issue Information

Dear Colleagues,

The noncoding genome harbors a complex array of noncoding biofeatures that regulate gene expression and play myriad roles in development and disease. Non-coding RNA is the most abundant non-coding biofeature, and long non-coding RNAs (lncRNAs) have been implicated as critical drivers or suppressors for many tumor types. LncRNAs have diverse functional roles in the cell. Some lncRNAs have been shown to exert local effects on gene expression, whereas others induce large-scale epigenetic remodelling to impact gene expression across a gene locus (e.g. HOTAIR) or whole chromosome (as is the case for XIST in X-chromosome dosage compensation). LncRNAs can also have roles in the post-transcriptional regulation of gene expression, such as MALAT1 in splicing and lincRNA-p21 in translation. LncRNA deregulation in cancer is pervasive, and the overexpression of oncogenic lncRNAs, or the inhibition of tumor suppressive lncRNAs can contribute to neoplasia. In addition, genome-wide association studies have implcated a select handful of lncRNAs as mediators of inherited susceptibility to cancer, and more recently, whole-genome sequencing analyses of tumors have identified somatic variants in lncRNAs that may contribute to the disease process. The functional validation of lncRNAs and lncRNA variants is essential, but challenging, as it is not currently possible to predict lncRNA activity based on transcript sequence alone. In recent years, novel technologies have emerged to allow the detailed mapping of ‘RNA interactomes—the RNA–RNA, RNA–DNA and RNA–protein interactions that characterize a transcript of interest. Cataloguing lncRNA interactomes is providing novel insight into the mechanistic roles of lncRNAs in cancer and will be critical in understanding the role of germline and somatic lncRNA variants associated with cancer.

Dr. Kate Lawrenson
Guest Editor

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Keywords

  • Long noncoding RNA
  • Transcriptomics
  • RNA-sequencing
  • Gene regulation

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Published Papers (6 papers)

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Research

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13 pages, 3645 KiB  
Article
Construction and Comprehensive Analysis of a Molecular Association Network via lncRNA–miRNA–Disease–Drug–Protein Graph
by Zhen-Hao Guo, Hai-Cheng Yi and Zhu-Hong You
Cells 2019, 8(8), 866; https://doi.org/10.3390/cells8080866 - 9 Aug 2019
Cited by 32 | Viewed by 5062
Abstract
One key issue in the post-genomic era is how to systematically describe the associations between small molecule transcripts or translations inside cells. With the rapid development of high-throughput “omics” technologies, the achieved ability to detect and characterize molecules with other molecule targets opens [...] Read more.
One key issue in the post-genomic era is how to systematically describe the associations between small molecule transcripts or translations inside cells. With the rapid development of high-throughput “omics” technologies, the achieved ability to detect and characterize molecules with other molecule targets opens the possibility of investigating the relationships between different molecules from a global perspective. In this article, a molecular association network (MAN) is constructed and comprehensively analyzed by integrating the associations among miRNA, lncRNA, protein, drug, and disease, in which any kind of potential associations can be predicted. More specifically, each node in MAN can be represented as a vector by combining two kinds of information including the attribute of the node itself (e.g., sequences of ncRNAs and proteins, semantics of diseases and molecular fingerprints of drugs) and the behavior of the node in the complex network (associations with other nodes). A random forest classifier is trained to classify and predict new interactions or associations between biomolecules. In the experiment, the proposed method achieved a superb performance with an area under curve (AUC) of 0.9735 under a five-fold cross-validation, which showed that the proposed method could provide new insight for exploration of the molecular mechanisms of disease and valuable clues for disease treatment. Full article
(This article belongs to the Special Issue lncRNA and Cancer)
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17 pages, 3335 KiB  
Article
Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas
by Tomasz Kolenda, Kacper Guglas, Magda Kopczyńska, Anna Teresiak, Renata Bliźniak, Andrzej Mackiewicz, Katarzyna Lamperska and Jacek Mackiewicz
Cells 2019, 8(4), 366; https://doi.org/10.3390/cells8040366 - 21 Apr 2019
Cited by 52 | Viewed by 5872
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we [...] Read more.
Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of ZFAS1 and its potential as a biomarker in HNSCC. Methods: The expression level of ZFAS1 in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the ZFAS1 expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. Results: The expression of ZFAS1 was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of ZFAS1 in HNSCCs compared to normal tissue samples. The ZFAS1 levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of ZFAS1 presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with ZFAS1, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of ZFAS1, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between ZFAS1 and its host gene, ZNFX1, was observed. The analysis of interactions indicated that ZFAS1 has a binding sequence for miR-150-5p. The expression of ZFAS1 and miR-150-5p is negatively correlated in HNSCC patients. miR-150-5p can regulate the 3′UTR of EIF4E mRNA. In the group of patients with high expression of ZFAS1 and low expression of miR-150-5p, we detected an up-regulation of EIF4E. Conclusions: In HNSCC, ZFAS1 displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients’ clinical outcomes. ZFAS1 likely regulates the cell phenotype through miR-150-5p and its downstream targets. Following further validation, ZFAS1 might prove a new and valuable biomarker. Full article
(This article belongs to the Special Issue lncRNA and Cancer)
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Review

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20 pages, 602 KiB  
Review
The Missing Lnc: The Potential of Targeting Triple-Negative Breast Cancer and Cancer Stem Cells by Inhibiting Long Non-Coding RNAs
by Justin M Brown, Marie-Claire D Wasson and Paola Marcato
Cells 2020, 9(3), 763; https://doi.org/10.3390/cells9030763 - 20 Mar 2020
Cited by 28 | Viewed by 5602
Abstract
Treatment decisions for breast cancer are based on staging and hormone receptor expression and include chemotherapies and endocrine therapy. While effective in many cases, some breast cancers are resistant to therapy, metastasize and recur, leading to eventual death. Higher percentages of tumor-initiating cancer [...] Read more.
Treatment decisions for breast cancer are based on staging and hormone receptor expression and include chemotherapies and endocrine therapy. While effective in many cases, some breast cancers are resistant to therapy, metastasize and recur, leading to eventual death. Higher percentages of tumor-initiating cancer stem cells (CSCs) may contribute to the increased aggressiveness, chemoresistance, and worse outcomes among breast cancer. This may be particularly true in triple-negative breast cancers (TNBCs) which have higher percentages of CSCs and are associated with worse outcomes. In recent years, increasing numbers of long non-coding RNAs (lncRNAs) have been identified as playing an important role in breast cancer progression and some of these have been specifically associated within the CSC populations of breast cancers. LncRNAs are non-protein-coding transcripts greater than 200 nucleotides which can have critical functions in gene expression regulation. The preclinical evidence regarding lncRNA antagonists for the treatment of cancer is promising and therefore, presents a potential novel approach for treating breast cancer and targeting therapy-resistant CSCs within these tumors. Herein, we summarize the lncRNAs that have been identified as functionally relevant in breast CSCs. Furthermore, our review of the literature and analysis of patient datasets has revealed that many of these breast CSC-associated lncRNAs are also enriched in TNBC. Together, this suggests that these lncRNAs may be playing a particularly important role in TNBC. Thus, certain breast cancer-promoting/CSC-associated lncRNAs could be targeted in the treatment of TNBCs and the CSCs within these tumors should be susceptible to anti-lncRNA therapy. Full article
(This article belongs to the Special Issue lncRNA and Cancer)
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21 pages, 835 KiB  
Review
Deciphering the Mounting Complexity of the p53 Regulatory Network in Correlation to Long Non-Coding RNAs (lncRNAs) in Ovarian Cancer
by Sonali Pal, Manoj Garg and Amit Kumar Pandey
Cells 2020, 9(3), 527; https://doi.org/10.3390/cells9030527 - 25 Feb 2020
Cited by 48 | Viewed by 6645
Abstract
Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational [...] Read more.
Amongst the various gynecological malignancies affecting female health globally, ovarian cancer is one of the predominant and lethal among all. The identification and functional characterization of long non-coding RNAs (lncRNAs) are made possible with the advent of RNA-seq and the advancement of computational logarithm in understanding human disease biology. LncRNAs can interact with deoxyribonucleic acid (DNA), ribonucleic acid (RNA), proteins and their combinations. Moreover, lncRNAs regulate orchestra of diverse functions including chromatin organization and transcriptional and post-transcriptional regulation. LncRNAs have conferred their critical role in key biological processes in human cancer including tumor initiation, proliferation, cell cycle, apoptosis, necroptosis, autophagy, and metastasis. The interwoven function of tumor-suppressor protein p53-linked lncRNAs in the ovarian cancer paradigm is of paramount importance. Several lncRNAs operate as p53 regulators or effectors and modulates a diverse array of functions either by participating in various signaling cascades or via interaction with different proteins. This review highlights the recent progress made in the identification of p53 associated lncRNAs while elucidating their molecular mechanisms behind the altered expression in ovarian cancer tumorigenesis. Moreover, the development of novel clinical and therapeutic strategies for targeting lncRNAs in human cancers harbors great promise. Full article
(This article belongs to the Special Issue lncRNA and Cancer)
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44 pages, 1931 KiB  
Review
Long Non-Coding RNA in the Pathogenesis of Cancers
by Yujing Chi, Di Wang, Junpei Wang, Weidong Yu and Jichun Yang
Cells 2019, 8(9), 1015; https://doi.org/10.3390/cells8091015 - 1 Sep 2019
Cited by 612 | Viewed by 18260
Abstract
The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic [...] Read more.
The incidence and mortality rate of cancer has been quickly increasing in the past decades. At present, cancer has become the leading cause of death worldwide. Most of the cancers cannot be effectively diagnosed at the early stage. Although there are multiple therapeutic treatments, including surgery, radiotherapy, chemotherapy, and targeted drugs, their effectiveness is still limited. The overall survival rate of malignant cancers is still low. It is necessary to further study the mechanisms for malignant cancers, and explore new biomarkers and targets that are more sensitive and effective for early diagnosis, treatment, and prognosis of cancers than traditional biomarkers and methods. Long non-coding RNAs (lncRNAs) are a class of RNA transcripts with a length greater than 200 nucleotides. Generally, lncRNAs are not capable of encoding proteins or peptides. LncRNAs exert diverse biological functions by regulating gene expressions and functions at transcriptional, translational, and post-translational levels. In the past decade, it has been demonstrated that the dysregulated lncRNA profile is widely involved in the pathogenesis of many diseases, including cancer, metabolic disorders, and cardiovascular diseases. In particular, lncRNAs have been revealed to play an important role in tumor growth and metastasis. Many lncRNAs have been shown to be potential biomarkers and targets for the diagnosis and treatment of cancers. This review aims to briefly discuss the latest findings regarding the roles and mechanisms of some important lncRNAs in the pathogenesis of certain malignant cancers, including lung, breast, liver, and colorectal cancers, as well as hematological malignancies and neuroblastoma. Full article
(This article belongs to the Special Issue lncRNA and Cancer)
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15 pages, 581 KiB  
Review
New Insights into the Interplay between Non-Coding RNAs and RNA-Binding Protein HnRNPK in Regulating Cellular Functions
by Yongjie Xu, Wei Wu, Qiu Han, Yaling Wang, Cencen Li, Pengpeng Zhang and Haixia Xu
Cells 2019, 8(1), 62; https://doi.org/10.3390/cells8010062 - 17 Jan 2019
Cited by 56 | Viewed by 8900
Abstract
The emerging data indicates that non-coding RNAs (ncRNAs) epresent more than the “junk sequences” of the genome. Both miRNAs and long non-coding RNAs (lncRNAs) are involved in fundamental biological processes, and their deregulation may lead to oncogenesis and other diseases. As an important [...] Read more.
The emerging data indicates that non-coding RNAs (ncRNAs) epresent more than the “junk sequences” of the genome. Both miRNAs and long non-coding RNAs (lncRNAs) are involved in fundamental biological processes, and their deregulation may lead to oncogenesis and other diseases. As an important RNA-binding protein (RBP), heterogeneous nuclear ribonucleoprotein K (hnRNPK) is known to regulate gene expression through the RNA-binding domain involved in various pathways, such as transcription, splicing, and translation. HnRNPK is a highly conserved gene that is abundantly expressed in mammalian cells. The interaction of hnRNPK and ncRNAs defines the novel way through which ncRNAs affect the expression of protein-coding genes and form autoregulatory feedback loops. This review summarizes the interactions of hnRNPK and ncRNAs in regulating gene expression at transcriptional and post-transcriptional levels or by changing the genomic structure, highlighting their involvement in carcinogenesis, glucose metabolism, stem cell differentiation, virus infection and other cellular functions. Drawing connections between such discoveries might provide novel targets to control the biological outputs of cells in response to different stimuli. Full article
(This article belongs to the Special Issue lncRNA and Cancer)
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