Special Issue "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 (15 June 2019)

Special Issue Editor

Guest Editor
Dr. Kate Lawrenson

Women’s Cancer Program at the Samuel Oschin Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, United States
Website 1 | Website 2 | E-Mail
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

Published Papers (2 papers)

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Research

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Open AccessArticle
Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas
Received: 19 February 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 21 April 2019
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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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Open AccessReview
New Insights into the Interplay between Non-Coding RNAs and RNA-Binding Protein HnRNPK in Regulating Cellular Functions
Received: 19 December 2018 / Revised: 8 January 2019 / Accepted: 15 January 2019 / Published: 17 January 2019
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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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