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Alternative Splicing in Cancer: Role, Mechanisms and Impact
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Alternative Splicing in Cancer: Role, Mechanisms and Impact

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (1 October 2022) | Viewed by 11080

Special Issue Editors

Dr. Christos K. Kontos

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Athens, Greece
Interests: colorectal cancer; leukemia; tumor biomarkers; anticancer drugs; apoptosis; BCL2 family; alternative splicing; kallikrein-related peptidases (KLKs); nanopore sequencing; next-generation sequencing (NGS)
Special Issues, Collections and Topics in MDPI journals
Dr. Pinelopi I. Artemaki

E-Mail Website
Guest Editor
Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens, Greece
Interests: alternative splicing; RNA biology; circular RNAs; pre-mRNAs; post-transcriptional analysis; apoptosis; BCL2 family; colorectal adenocarcinoma; molecular biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Alternative splicing is a key biological process in human cells, as primary transcripts from more than 95% of human multi-exon genes are subjected to alternative splicing during their post-transcriptional maturation. Due to its key role, its deregulation has been characterized as one of the hallmarks of cancer, while its targeting is considered a promising therapeutic strategy. The current Special Issue aims to present new information regarding the mechanisms and/or roles of alternative splicing, which could lead to the development and/or progression of malignancies, or resistance to anticancer therapy. Moreover, this Special Issue will focus on the products of alternative splicing—particularly on their identity, biological role, and/or clinical utility. Authors are encouraged to submit their original research studies concerning this topic. Review articles will also be taken into consideration. The Guest Editors are also willing to evaluate manuscripts describing other aspects of alternative splicing.

Dr. Christos K. Kontos
Dr. Pinelopi I. Artemaki
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. 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.

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Published Papers (3 papers)

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Research

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22 pages, 4986 KiB  
Article
A Regulatory Axis between Epithelial Splicing Regulatory Proteins and Estrogen Receptor α Modulates the Alternative Transcriptome of Luminal Breast Cancer
by Jamal Elhasnaoui, Giulio Ferrero, Valentina Miano, Lorenzo Franchitti, Isabella Tarulli, Lucia Coscujuela Tarrero, Santina Cutrupi and Michele De Bortoli
Int. J. Mol. Sci. 2022, 23(14), 7835; https://doi.org/10.3390/ijms23147835 - 16 Jul 2022
Cited by 6 | Viewed by 3300
Abstract
Epithelial splicing regulatory proteins 1 and 2 (ESRP1/2) control the splicing pattern during epithelial to mesenchymal transition (EMT) in a physiological context and in cancer, including breast cancer (BC). Here, we report that ESRP1, but not ESRP2, is overexpressed in luminal [...] Read more.
Epithelial splicing regulatory proteins 1 and 2 (ESRP1/2) control the splicing pattern during epithelial to mesenchymal transition (EMT) in a physiological context and in cancer, including breast cancer (BC). Here, we report that ESRP1, but not ESRP2, is overexpressed in luminal BCs of patients with poor prognosis and correlates with estrogen receptor α (ERα) levels. Analysis of ERα genome-binding profiles in cell lines and primary breast tumors showed its binding in the proximity of ESRP1 and ESRP2 genes, whose expression is strongly decreased by ERα silencing in hormone-deprived conditions. The combined knock-down of ESRP1/2 in MCF-7 cells followed by RNA-Seq, revealed the dysregulation of 754 genes, with a widespread alteration of alternative splicing events (ASEs) of genes involved in cell signaling, metabolism, cell growth, and EMT. Functional network analysis of ASEs correlated with ESRP1/2 expression in ERα+ BCs showed RAC1 as the hub node in the protein–protein interactions altered by ESRP1/2 silencing. The comparison of ERα- and ESRP-modulated ASEs revealed 63 commonly regulated events, including 27 detected in primary BCs and endocrine-resistant cell lines. Our data support a functional implication of the ERα-ESRP1/2 axis in the onset and progression of BC by controlling the splicing patterns of related genes. Full article
(This article belongs to the Special Issue Alternative Splicing in Cancer: Role, Mechanisms and Impact)
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17 pages, 4804 KiB  
Article
Cytoprotective Activity of Polyamines Is Associated with the Alternative Splicing of RAD51A Pre-mRNA in Normal Human CD4+ T Lymphocytes
by Yulia A. Gladilina, Lylia Bey, Abdullah Hilal, Ekaterina V. Neborak, Varvara G. Blinova and Dmitry D. Zhdanov
Int. J. Mol. Sci. 2022, 23(3), 1863; https://doi.org/10.3390/ijms23031863 - 7 Feb 2022
Cited by 5 | Viewed by 2933
Abstract
Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have [...] Read more.
Physiological polyamines are ubiquitous polycations with pleiotropic biochemical activities, including regulation of gene expression and cell proliferation as well as modulation of cell signaling. They can also decrease DNA damage and promote cell survival. In the present study, we demonstrated that polyamines have cytoprotective effects on normal human CD4+ T lymphocytes but not on cancer Jurkat or K562 cells. Pretreatment of lymphocytes with polyamines resulted in a significant reduction in cells with DNA damage induced by doxorubicin, cisplatin, or irinotecan, leading to an increase in cell survival and viability. The induction of RAD51A expression was in response to DNA damage in both cancer and normal cells. However, in normal cells, putrescin pretreatment resulted in alternative splicing of RAD51A and the switch of the predominant expression from the splice variant with the deletion of exon 4 to the full-length variant. Induction of RAD51A alternative splicing by splice-switching oligonucleotides resulted in a decrease in DNA damage and cell protection against cisplatin-induced apoptosis. The results of this study suggest that the cytoprotective activity of polyamines is associated with the alternative splicing of RAD51A pre-mRNA in normal human CD4+ T lymphocytes. The difference in the sensitivity of normal and cancer cells to polyamines may become the basis for the use of these compounds to protect normal lymphocytes during lymphoblastic chemotherapy. Full article
(This article belongs to the Special Issue Alternative Splicing in Cancer: Role, Mechanisms and Impact)
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Review

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27 pages, 1641 KiB  
Review
Integration of TE Induces Cancer Specific Alternative Splicing Events
by Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Woo Hyeon Bae, Du Hyeong Lee and Heui-Soo Kim
Int. J. Mol. Sci. 2022, 23(18), 10918; https://doi.org/10.3390/ijms231810918 - 18 Sep 2022
Cited by 4 | Viewed by 3954
Abstract
Alternative splicing of messenger RNA (mRNA) precursors contributes to genetic diversity by generating structurally and functionally distinct transcripts. In a disease state, alternative splicing promotes incidence and development of several cancer types through regulation of cancer-related biological processes. Transposable elements (TEs), having the [...] Read more.
Alternative splicing of messenger RNA (mRNA) precursors contributes to genetic diversity by generating structurally and functionally distinct transcripts. In a disease state, alternative splicing promotes incidence and development of several cancer types through regulation of cancer-related biological processes. Transposable elements (TEs), having the genetic ability to jump to other regions of the genome, can bring about alternative splicing events in cancer. TEs can integrate into the genome, mostly in the intronic regions, and induce cancer-specific alternative splicing by adjusting various mechanisms, such as exonization, providing splicing donor/acceptor sites, alternative regulatory sequences or stop codons, and driving exon disruption or epigenetic regulation. Moreover, TEs can produce microRNAs (miRNAs) that control the proportion of transcripts by repressing translation or stimulating the degradation of transcripts at the post-transcriptional level. Notably, TE insertion creates a cancer-friendly environment by controlling the overall process of gene expression before and after transcription in cancer cells. This review emphasizes the correlative interaction between alternative splicing by TE integration and cancer-associated biological processes, suggesting a macroscopic mechanism controlling alternative splicing by TE insertion in cancer. Full article
(This article belongs to the Special Issue Alternative Splicing in Cancer: Role, Mechanisms and Impact)
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