Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.4
5.2
Journals
Cancers
Special Issues
Alterations in Cis-Regulatory Elements and Non-Coding RNAs in Human Cancer
share announcement

Alterations in Cis-Regulatory Elements and Non-Coding RNAs in Human Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 8019

Special Issue Editors

Prof. Dr. Tamar Juven-Gershon

E-Mail Website
Guest Editor
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel
Interests: RNA polymerase II transcription; core promoters; gene expression in cancer; molecular biology; developmental biology
Dr. Philipp Bucher

E-Mail Website
Guest Editor
SIB Swiss Institute of Bioinformatics, Unil, Quartier Sorge - Amphipôle, 1015 Lausanne, Switzerland
Interests: transcription factors; cis-regulatory elements; cancer epigenomics; computational biology

Special Issue Information

Dear Colleagues,

For many years, studies of human cancer have mainly focused on cancer-associated mutations within protein-coding sequences. Nevertheless, the vast majority of the genome, which is non-coding, is involved in the regulation of gene expression. Indeed, in addition to the few previously characterized non-coding driver mutations (including the extensively studied mutations in the TERT promoter), recent findings by the Pan-Cancer Analysis of Whole Genomes (PCAWG) project of the International Cancer Genome Consortium (ICGC) have demonstrated the existence of multiple non-coding somatic mutations in cancer genomes. This Special Issue will address follow-up, as well as independent, studies that focus on the identification and characterization of alterations in cis-regulatory elements (both genetic and epigenetic) in human cancer, with particular emphasis on enhancers, promoters, transcription factor binding sites, and non-coding RNAs.

Prof. Dr. Tamar Juven-Gershon
Dr. Philipp Bucher
Guest Editors

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. Cancers 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 2900 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.

Keywords

  • enhancers
  • promoters
  • CpG islands
  • epigenetic aberrant histone modifications
  • DNA methylation
  • allele-specific expression
  • cancer-driving cis-regulatory elements
  • cancer-specific promoters and transcription factor binding sites
  • retro-elements induced gene expression
  • cis-regulatory mutations in tumor progression and treatment resistance
  • epigenetic changes in metastasis formation and disease progression
  • non-coding mutations and single nucleotide variations as biomarkers
  • whole-genome sequencing for personalized cancer treatment
  • bioinformatic interpretation of cancer genomes
  • alternative splicing in cancer
  • alteration of non-coding RNA structure and expression
  • epigenetic biomarkers

Published Papers (3 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

25 pages, 11396 KiB  
Article
Association of MGMT Promoter and Enhancer Methylation with Genetic Variants, Clinical Parameters, and Demographic Characteristics in Glioblastoma
by Katja Zappe, Katharina Pühringer, Simon Pflug, Daniel Berger, Serge Weis, Sabine Spiegl-Kreinecker and Margit Cichna-Markl
Cancers 2023, 15(24), 5777; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15245777 - 09 Dec 2023
Viewed by 799
Abstract
The response of glioblastoma (GBM) patients to the alkylating agent temozolomide (TMZ) vitally depends on the expression level of the repair protein O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT is strongly regulated by promoter methylation, the methylation status of the MGMT promoter has emerged as [...] Read more.
The response of glioblastoma (GBM) patients to the alkylating agent temozolomide (TMZ) vitally depends on the expression level of the repair protein O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT is strongly regulated by promoter methylation, the methylation status of the MGMT promoter has emerged as a prognostic and predictive biomarker for GBM patients. By determining the methylation levels of the four enhancers located within or close to the MGMT gene, we recently found that enhancer methylation contributes to MGMT regulation. In this study, we investigated if methylation of the four enhancers is associated with SNP rs16906252, TERT promoter mutations C228T and C250T, TERT SNP rs2853669, proliferation index Ki-67, overall survival (OS), age, and sex of the patients. In general, associations with genetic variants, clinical parameters, and demographic characteristics were caused by a complex interplay of multiple CpGs in the MGMT promoter and of multiple CpGs in enhancer regions. The observed associations for intragenic enhancer 4, located in intron 2 of MGMT, differed from associations observed for the three intergenic enhancers. Some findings were restricted to subgroups of samples with either methylated or unmethylated MGMT promoters, underpinning the relevance of the MGMT promoter status in GBMs. Full article
(This article belongs to the Special Issue Alterations in Cis-Regulatory Elements and Non-Coding RNAs in Human Cancer)
►▼ Show Figures

Figure 1

17 pages, 2825 KiB  
Article
Enhancer Clusters Drive Type I Interferon-Induced TRAIL Overexpression in Cancer, and Its Intracellular Protein Accumulation Fails to Induce Apoptosis
by Carolina Di Benedetto, Taimoor Khan, Santiago Serrano-Saenz, Anthony Rodriguez-Lemus, Chananat Klomsiri, Tim-Mathis Beutel, Alysia Thach, Henning Walczak and Paola Betancur
Cancers 2023, 15(3), 967; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030967 - 03 Feb 2023
Viewed by 2151
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine produced and secreted by immune cells in response to an infection, often in response to interferon (IFN) stimulation. In cancer, it has also been shown that IFN stimulates the production of TRAIL, and it [...] Read more.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine produced and secreted by immune cells in response to an infection, often in response to interferon (IFN) stimulation. In cancer, it has also been shown that IFN stimulates the production of TRAIL, and it has been proposed that this TRAIL can induce apoptosis in an autocrine or paracrine manner in different cancer cells. Yet, the mechanism mediating TRAIL upregulation and the implications of TRAIL as an apoptotic molecule in cancer cells are still poorly understood. We show here that in certain cancer cells, TRAIL is upregulated by enhancer clusters, potent genomic regulatory regions containing densely packed enhancers that have combinatorial and additive activity and that are usually found to be associated with cancer-promoting genes. Moreover, we found that TRAIL upregulation by IFNα is mediated by these enhancer clusters in breast and lung cancer cells. Surprisingly, IFNα stimulation leads to the intracellular accumulation of TRAIL protein in these cancer cells. Consequently, this TRAIL is not capable of inducing apoptosis. Our study provides novel insights into the mechanism behind the interferon-mediated upregulation of TRAIL and its protein accumulation in cancer cells. Further investigation is required to understand the role of intracellular TRAIL or depict the mechanisms mediating its apoptosis impairment in cancer cells. Full article
(This article belongs to the Special Issue Alterations in Cis-Regulatory Elements and Non-Coding RNAs in Human Cancer)
►▼ Show Figures

Figure 1

28 pages, 5815 KiB  
Article
Enhancer RNA Transcription Is Essential for a Novel CSF1 Enhancer in Triple-Negative Breast Cancer
by Michael W. Lewis, Kamila Wisniewska, Caitlin M. King, Shen Li, Alisha Coffey, Michael R. Kelly, Matthew J. Regner and Hector L. Franco
Cancers 2022, 14(7), 1852; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071852 - 06 Apr 2022
Cited by 4 | Viewed by 4244
Abstract
Enhancers are critical regulatory elements in the genome that help orchestrate spatiotemporal patterns of gene expression during development and normal physiology. In cancer, enhancers are often rewired by various genetic and epigenetic mechanisms for the activation of oncogenes that lead to initiation and [...] Read more.
Enhancers are critical regulatory elements in the genome that help orchestrate spatiotemporal patterns of gene expression during development and normal physiology. In cancer, enhancers are often rewired by various genetic and epigenetic mechanisms for the activation of oncogenes that lead to initiation and progression. A key feature of active enhancers is the production of non-coding RNA molecules called enhancer RNAs, whose functions remain unknown but can be used to specify active enhancers de novo. Using a combination of eRNA transcription and chromatin modifications, we have identified a novel enhancer located 30 kb upstream of Colony Stimulating Factor 1 (CSF1). Notably, CSF1 is implicated in the progression of breast cancer, is overexpressed in triple-negative breast cancer (TNBC) cell lines, and its enhancer is primarily active in TNBC patient tumors. Genomic deletion of the enhancer (via CRISPR/Cas9) enabled us to validate this regulatory element as a bona fide enhancer of CSF1 and subsequent cell-based assays revealed profound effects on cancer cell proliferation, colony formation, and migration. Epigenetic silencing of the enhancer via CRISPR-interference assays (dCas9-KRAB) coupled to RNA-sequencing, enabled unbiased identification of additional target genes, such as RSAD2, that are predictive of clinical outcome. Additionally, we repurposed the RNA-guided RNA-targeting CRISPR-Cas13 machinery to specifically degrade the eRNAs transcripts produced at this enhancer to determine the consequences on CSF1 mRNA expression, suggesting a post-transcriptional role for these non-coding transcripts. Finally, we test our eRNA-dependent model of CSF1 enhancer function and demonstrate that our results are extensible to other forms of cancer. Collectively, this work describes a novel enhancer that is active in the TNBC subtype, which is associated with cellular growth, and requires eRNA transcripts for proper enhancer function. These results demonstrate the significant impact of enhancers in cancer biology and highlight their potential as tractable targets for therapeutic intervention. Full article
(This article belongs to the Special Issue Alterations in Cis-Regulatory Elements and Non-Coding RNAs in Human Cancer)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-3
Back to TopTop