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Biomolecules
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10th Anniversary of Biomolecules—Recent Advances in Understanding of Molecular Pathology...
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10th Anniversary of Biomolecules—Recent Advances in Understanding of Molecular Pathology and Therapeutics of Cancer

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 10702

Special Issue Editors

Prof. Dr. Prakash Kulkarni

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Guest Editor
Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA, USA
Interests: cancer systems biology; evolution; non-genetic mechanisms; intrinsically disordered proteins
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Vladimir N. Uversky

grade E-Mail Website
Guest Editor
Department of Molecular Medicine, USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC07, Tampa, FL 33612, USA
Interests: intrinsically disordered proteins; protein folding; protein misfolding; partially folded proteins; protein aggregation; protein structure; protein function; protein stability; protein biophysics; protein bioinformatics; conformational diseases; protein–ligand interactions; protein–protein interactions; liquid-liquid phase transitions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In 2020, the journal Biomolecules is celebrating its 10th anniversary. To celebrate this important occasion, we are delighted and proud to celebrate with a series of Special Issues and events. To date, the journal has received more than 6,000 contributions and published more than 2,600 articles, and the journal website attracts more than 200 thousands monthly page views. We would like to express our sincerest thanks to our readers, innumerable authors, anonymous peer reviewers, editors, and all the people working in some way for the journal who have made substantial contributions for years. Without your support, we would never have made it.

To mark this important milestone, a Special Issue entitled “10th Anniversary of Biomolecules—Recent Advances in Understanding of Molecular Pathology and Therapeutics of Cancer” is being launched. This Special Issue will collect research articles, and high-quality review papers in the research fields relating to this theme. We kindly encourage research groups working in various areas of cancer to make contributions to this Special Issue.

A scientific journal is the collaborative achievement of many scientists from all over the world and we would like to thank all our authors and reviewers who have contributed to the Special Issue for their support. In recognition of our authors’ continued support, Biomolecules is pleased to announce that the “Biomolecules Best Paper Awards for Anniversary Special Issues” will be launched and granted to the best papers published in the the Anniversary Special Issues. See details at:

https://www.mdpi.com/journal/biomolecules/awards

text

Prof. Dr. Prakash Kulkarni
Dr. Vladimir N. Uversky
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. Biomolecules is an international peer-reviewed open access monthly 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 2700 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.

Published Papers (3 papers)

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Research

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14 pages, 5406 KiB  
Article
A Novel Splice Variant of the Inhibitor of Growth 3 Lacks the Plant Homeodomain and Regulates Epithelial–Mesenchymal Transition in Prostate Cancer Cells
by Anna Melekhova, Mirjam Leeder, Thanakorn Pungsrinont, Tim Schmäche, Julia Kallenbach, Marzieh Ehsani, Kimia Mirzakhani, Seyed Mohammad Mahdi Rasa, Francesco Neri and Aria Baniahmad
Biomolecules 2021, 11(8), 1152; https://doi.org/10.3390/biom11081152 - 04 Aug 2021
Cited by 5 | Viewed by 3054
Abstract
Inhibitor of growth 3 (ING3) is one of five members of the ING tumour suppressor family, characterized by a highly conserved plant homeodomain (PHD) as a reader of the histone mark H3K4me3. ING3 was reported to act as a tumour suppressor in many [...] Read more.
Inhibitor of growth 3 (ING3) is one of five members of the ING tumour suppressor family, characterized by a highly conserved plant homeodomain (PHD) as a reader of the histone mark H3K4me3. ING3 was reported to act as a tumour suppressor in many different cancer types to regulate apoptosis. On the other hand, ING3 levels positively correlate with poor survival prognosis of prostate cancer (PCa) patients. In PCa cells, ING3 acts rather as an androgen receptor (AR) co-activator and harbours oncogenic properties in PCa. Here, we show the identification of a novel ING3 splice variant in both the human PCa cell line LNCaP and in human PCa patient specimen. The novel ING3 splice variant lacks exon 11, ING3∆ex11, which results in deletion of the PHD, providing a unique opportunity to analyse functionally the PHD of ING3 by a natural splice variant. Functionally, overexpression of ING3Δex11 induced morphological changes of LNCaP-derived 3D spheroids with generation of lumen and pore-like structures within spheroids. Since these structures are an indicator of epithelial–mesenchymal transition (EMT), key regulatory factors and markers for EMT were analysed. The data suggest that in contrast to ING3, ING3Δex11 specifically modulates the expression of key EMT-regulating upstream transcription factors and induces the expression of EMT markers, indicating that the PHD of ING3 inhibits EMT. In line with this, ING3 knockdown also induced the expression of EMT markers, confirming the impact of ING3 on EMT regulation. Further, ING3 knockdown induced cellular senescence via a pathway leading to cell cycle arrest, indicating an oncogenic role for ING3 in PCa. Thus, the data suggest that the ING3Δex11 splice variant lacking functional PHD exhibits oncogenic characteristics through triggering EMT in PCa cells. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomolecules—Recent Advances in Understanding of Molecular Pathology and Therapeutics of Cancer)
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21 pages, 4672 KiB  
Article
Mutations of Intrinsically Disordered Protein Regions Can Drive Cancer but Lack Therapeutic Strategies
by Bálint Mészáros, Borbála Hajdu-Soltész, András Zeke and Zsuzsanna Dosztányi
Biomolecules 2021, 11(3), 381; https://doi.org/10.3390/biom11030381 - 04 Mar 2021
Cited by 23 | Viewed by 3249
Abstract
Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting [...] Read more.
Many proteins contain intrinsically disordered regions (IDRs) which carry out important functions without relying on a single well-defined conformation. IDRs are increasingly recognized as critical elements of regulatory networks and have been also associated with cancer. However, it is unknown whether mutations targeting IDRs represent a distinct class of driver events associated with specific molecular and system-level properties, cancer types and treatment options. Here, we used an integrative computational approach to explore the direct role of intrinsically disordered protein regions driving cancer. We showed that around 20% of cancer drivers are primarily targeted through a disordered region. These IDRs can function in multiple ways which are distinct from the functional mechanisms of ordered drivers. Disordered drivers play a central role in context-dependent interaction networks and are enriched in specific biological processes such as transcription, gene expression regulation and protein degradation. Furthermore, their modulation represents an alternative mechanism for the emergence of all known cancer hallmarks. Importantly, in certain cancer patients, mutations of disordered drivers represent key driving events. However, treatment options for such patients are currently severely limited. The presented study highlights a largely overlooked class of cancer drivers associated with specific cancer types that need novel therapeutic options. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomolecules—Recent Advances in Understanding of Molecular Pathology and Therapeutics of Cancer)
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Review

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15 pages, 1532 KiB  
Review
Pregnane X Receptor (PXR) Polymorphisms and Cancer Treatment
by Aikaterini Skandalaki, Panagiotis Sarantis and Stamatios Theocharis
Biomolecules 2021, 11(8), 1142; https://doi.org/10.3390/biom11081142 - 02 Aug 2021
Cited by 13 | Viewed by 3196
Abstract
Pregnane X Receptor (PXR) belongs to the nuclear receptors’ superfamily and mainly functions as a xenobiotic sensor activated by a variety of ligands. PXR is widely expressed in normal and malignant tissues. Drug metabolizing enzymes and transporters are also under PXR’s regulation. Antineoplastic [...] Read more.
Pregnane X Receptor (PXR) belongs to the nuclear receptors’ superfamily and mainly functions as a xenobiotic sensor activated by a variety of ligands. PXR is widely expressed in normal and malignant tissues. Drug metabolizing enzymes and transporters are also under PXR’s regulation. Antineoplastic agents are of particular interest since cancer patients are characterized by significant intra-variability to treatment response and severe toxicities. Various PXR polymorphisms may alter the function of the protein and are linked with significant effects on the pharmacokinetics of chemotherapeutic agents and clinical outcome variability. The purpose of this review is to summarize the roles of PXR polymorphisms in the metabolism and pharmacokinetics of chemotherapeutic drugs. It is also expected that this review will highlight the importance of PXR polymorphisms in selection of chemotherapy, prediction of adverse effects and personalized medicine. Full article
(This article belongs to the Special Issue 10th Anniversary of Biomolecules—Recent Advances in Understanding of Molecular Pathology and Therapeutics of Cancer)
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