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Article ; Online: UBE2T promotes β-catenin nuclear translocation in hepatocellular carcinoma through MAPK/ERK-dependent activation.

Lioulia, Elisavet / Mokos, Panagiotis / Panteris, Emmanuel / Dafou, Dimitra

2022 Volume 16, Issue 8, Page(s) 1694–1713

Abstract: Ubiquitin-conjugating enzyme E2T (UBE2T) has been implicated in many types of cancer including hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) process plays a fundamental role during tumor metastasis and progression. However, the ... ...

Abstract	Ubiquitin-conjugating enzyme E2T (UBE2T) has been implicated in many types of cancer including hepatocellular carcinoma (HCC). Epithelial-mesenchymal transition (EMT) process plays a fundamental role during tumor metastasis and progression. However, the molecular mechanisms underlying EMT in HCC in accordance with UBE2T still remain unknown. In this study, we showed that UBE2T overexpression augmented the oncogenic properties and specifically EMT in HCC cell lines, while its silencing attenuated them. UBE2T affected the activation of EMT-associated signaling pathways: MAPK/ERK, AKT/mTOR, and Wnt/β-catenin. In addition, we revealed that the epithelial protein complex of E-cadherin/β-catenin, a vital regulator of signal transduction in tumor initiation and progression, was totally disrupted at the cell membrane. In particular, we observed that UBE2T overexpression led to E-cadherin loss accompanied by a simultaneous elevation of both cytoplasmic and nuclear β-catenin, while its silencing resulted in a strong E-cadherin turnover at the cell membrane. Interestingly, chemical inhibition of the MAPK/ERK, AKT/mTOR, and Wnt/β-catenin signaling pathways demonstrated that the nuclear translocation of β-catenin and subsequent EMT was enhanced mainly by MAPK/ERK. Collectively, our findings demonstrate the UBE2T/MAPK-ERK/β-catenin axis as a critical regulator of cell state transition and EMT in HCC.
MeSH term(s)	Cadherins ; Carcinoma, Hepatocellular/pathology ; Cell Line, Tumor ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Humans ; Liver Neoplasms/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Ubiquitin-Conjugating Enzymes/genetics ; Ubiquitin-Conjugating Enzymes/metabolism ; Wnt Signaling Pathway ; beta Catenin/metabolism
Chemical Substances	Cadherins ; beta Catenin ; UBE2T protein, human (EC 2.3.2.23) ; Ubiquitin-Conjugating Enzymes (EC 2.3.2.23) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TOR Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2022-03-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13111
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Article: Association of Matrix Metalloproteinase (MMP) Gene Polymorphisms With Knee Osteoarthritis: A Review of the Literature.

Milaras, Christos / Lepetsos, Panagiotis / Dafou, Dimitra / Potoupnis, Michael / Tsiridis, Eleftherios

Cureus

2021 Volume 13, Issue 10, Page(s) e18607

Abstract: Progressive matrix metalloproteinase (MMP)-induced degradation of the extracellular matrix (ECM) of the articular cartilage is one of the major pathogenic osteoarthritis (OA) events. Several single nucleotide polymorphisms (SNPs) in genes encoding MMPs ... ...

Abstract	Progressive matrix metalloproteinase (MMP)-induced degradation of the extracellular matrix (ECM) of the articular cartilage is one of the major pathogenic osteoarthritis (OA) events. Several single nucleotide polymorphisms (SNPs) in genes encoding MMPs have been identified as affecting MMP expression, production, and enzymatic activity. This study systematically reviews the literature regarding the association between the SNPs of genes encoding MMPs and the risk of knee OA. An electronic search in the PubMed and Web of Science databases from conception to January 2021 was performed addressing studies relating MMPs genetic polymorphisms with the risk of knee OA. We included case-control studies that used validated genotyping methods to detect the SNPs' association in MMP genes with primary knee OA risk. Ten studies were finally included in this systematic review, evaluating different SNPs in six MMP genes in terms of knee OA pathogenesis: MMP-1 (3 SNPs), MMP-2 (1 SNP), MMP-3 (9 SNPs), MMP-8 (10 SNPs), MMP-9 (6 SNPs), and MMP-13 (1 SNP). Among them, nine SNPs of four MMP genes have been associated with knee OA: (a) MMP-1 -1607 1G/2G (Turkish, Chinese), (b) MMP-3 rs650108, rs650108, rs520540, rs602128, rs679620 (Chinese), (c) MMP-8 rs1940475 and rs376520 (Finnish), and (d) MMP-13 77A/ (rs2252070) (Chinese). The present review summarizes all known SNPs of MMP genes related to a higher risk of knee OA. There are at least nine SNPs in four MMP genes associated with knee OA. No solid correlation between MMP genotype and knee OA phenotype exists. More high-quality studies and modern genetic testing methods are needed to fully elucidate the role of polymorphisms of MMP genes in knee OA pathogenesis.
Language	English
Publishing date	2021-10-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.18607
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Article: Inactivation of Tumor Suppressor CYLD Inhibits Fibroblast Reprogramming to Pluripotency.

Bekas, Nikolaos / Samiotaki, Martina / Papathanasiou, Maria / Mokos, Panagiotis / Pseftogas, Athanasios / Xanthopoulos, Konstantinos / Thanos, Dimitris / Mosialos, George / Dafou, Dimitra

Cancers

2023 Volume 15, Issue 20

Abstract: ... ...

Abstract	CYLD
Language	English
Publishing date	2023-10-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15204997
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Article ; Online: Gene targeting in amyotrophic lateral sclerosis using causality-based feature selection and machine learning.

Founta, Kyriaki / Dafou, Dimitra / Kanata, Eirini / Sklaviadis, Theodoros / Zanos, Theodoros P / Gounaris, Anastasios / Xanthopoulos, Konstantinos

Molecular medicine (Cambridge, Mass.)

2023 Volume 29, Issue 1, Page(s) 12

Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease that affects upper and lower motor neurons. As the molecular basis of the disease is still elusive, the development of high-throughput sequencing ... ...

Abstract	Background: Amyotrophic lateral sclerosis (ALS) is a rare progressive neurodegenerative disease that affects upper and lower motor neurons. As the molecular basis of the disease is still elusive, the development of high-throughput sequencing technologies, combined with data mining techniques and machine learning methods, could provide remarkable results in identifying pathogenetic mechanisms. High dimensionality is a major problem when applying machine learning techniques in biomedical data analysis, since a huge number of features is available for a limited number of samples. The aim of this study was to develop a methodology for training interpretable machine learning models in the classification of ALS and ALS-subtypes samples, using gene expression datasets. Methods: We performed dimensionality reduction in gene expression data using a semi-automated preprocessing systematic gene selection procedure using Statistically Equivalent Signature (SES), a causality-based feature selection algorithm, followed by Boosted Regression Trees (XGBoost) and Random Forest to train the machine learning classifiers. The SHapley Additive exPlanations (SHAP values) were used for interpretation of the machine learning classifiers. The methodology was developed and tested using two distinct publicly available ALS RNA-seq datasets. We evaluated the performance of SES as a dimensionality reduction method against: (a) Least Absolute Shrinkage and Selection Operator (LASSO), and (b) Local Outlier Factor (LOF). Results: The proposed methodology achieved 85.18% accuracy for the classification of cerebellum or frontal cortex samples as C9orf72-related familial ALS, sporadic ALS or healthy samples. Importantly, the genes identified as the most determinative have also been reported as disease-associated in ALS literature. When tested in the evaluation dataset, the methodology achieved 88.89% accuracy for the classification of sporadic ALS motor neuron samples. When LASSO was used as feature selection method instead of SES, the accuracy of the machine learning classifiers ranged from 74.07 to 96.30%, depending on tissue assessed, while LOF underperformed significantly (77.78% accuracy for the classification of pooled cerebellum and frontal cortex samples). Conclusions: Using SES, we addressed the challenge of high dimensionality in gene expression data analysis, and we trained accurate machine learning ALS classifiers, specific for the gene expression patterns of different disease subtypes and tissue samples, while identifying disease-associated genes.
MeSH term(s)	Humans ; Amyotrophic Lateral Sclerosis/genetics ; Neurodegenerative Diseases ; Machine Learning ; Gene Targeting
Language	English
Publishing date	2023-01-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1283676-x
ISSN	1528-3658 ; 1076-1551
ISSN (online)	1528-3658
ISSN	1076-1551
DOI	10.1186/s10020-023-00603-y
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Article ; Online: HPV16

Konstantopoulos, Georgios / Leventakou, Danai / Saltiel, Despoina-Rozi / Zervoudi, Efthalia / Logotheti, Eirini / Pettas, Spyros / Karagianni, Korina / Daiou, Angeliki / Hatzistergos, Konstantinos E / Dafou, Dimitra / Arsenakis, Minas / Kottaridi, Christine

Viruses

2024 Volume 16, Issue 1

Abstract: Human Papillomaviruses have been associated with the occurrence of cervical cancer, the fourth most common cancer that affects women globally, while 70% of cases are caused by infection with the high-risk types HPV16 and HPV18. The integration of these ... ...

Abstract	Human Papillomaviruses have been associated with the occurrence of cervical cancer, the fourth most common cancer that affects women globally, while 70% of cases are caused by infection with the high-risk types HPV16 and HPV18. The integration of these viruses' oncogenes
MeSH term(s)	Female ; Humans ; B7-H1 Antigen/genetics ; Human papillomavirus 16/genetics ; Immune Evasion ; MicroRNAs/genetics ; Uterine Cervical Neoplasms/genetics ; Uterine Cervical Neoplasms/virology ; Oncogene Proteins, Viral/genetics
Chemical Substances	B7-H1 Antigen ; MicroRNAs ; MIRN143 microRNA, human ; E6 protein, Human papillomavirus type 16 ; Oncogene Proteins, Viral ; HIF1A protein, human
Language	English
Publishing date	2024-01-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16010113
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Article ; Online: Αnti-prion effects of anthocyanins.

Christoudia, Nikoletta / Bekas, Nikolaos / Kanata, Eirini / Chatziefsthathiou, Athanasia / Pettas, Spyros / Karagianni, Korina / Da Silva Correia, Susana Margarida / Schmitz, Matthias / Zerr, Inga / Tsamesidis, Ioannis / Xanthopoulos, Konstantinos / Dafou, Dimitra / Sklaviadis, Theodoros

Redox biology

2024 Volume 72, Page(s) 103133

Abstract: Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, ...

Abstract	Prion diseases, also known as Transmissible Spongiform Encephalopathies (TSEs), are protein-based neurodegenerative disorders (NDs) affecting humans and animals. They are characterized by the conformational conversion of the normal cellular prion protein, PrP
MeSH term(s)	Anthocyanins/pharmacology ; Anthocyanins/chemistry ; Humans ; Reactive Oxygen Species/metabolism ; NF-E2-Related Factor 2/metabolism ; Antioxidants/pharmacology ; Prion Diseases/drug therapy ; Prion Diseases/metabolism ; Prion Diseases/pathology ; Kelch-Like ECH-Associated Protein 1/metabolism ; Animals ; PrPSc Proteins/metabolism ; Signal Transduction/drug effects
Chemical Substances	Anthocyanins ; Reactive Oxygen Species ; NF-E2-Related Factor 2 ; Antioxidants ; Kelch-Like ECH-Associated Protein 1 ; PrPSc Proteins ; NFE2L2 protein, human ; KEAP1 protein, human
Language	English
Publishing date	2024-03-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2024.103133
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Article ; Online: A Systematic Review of Common and Brain-Disease-Specific RNA Editing Alterations Providing Novel Insights into Neurological and Neurodegenerative Disease Manifestations.

Karagianni, Korina / Pettas, Spyros / Christoforidou, Georgia / Kanata, Eirini / Bekas, Nikolaos / Xanthopoulos, Konstantinos / Dafou, Dimitra / Sklaviadis, Theodoros

Biomolecules

2022 Volume 12, Issue 3

Abstract: RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common ... ...

Abstract	RNA editing contributes to transcriptome diversification through RNA modifications in relation to genome-encoded information (RNA-DNA differences, RDDs). The deamination of Adenosine (A) to Inosine (I) or Cytidine (C) to Uridine (U) is the most common type of mammalian RNA editing. It occurs as a nuclear co- and/or post-transcriptional event catalyzed by ADARs (Adenosine deaminases acting on RNA) and APOBECs (apolipoprotein B mRNA editing enzyme catalytic polypeptide-like genes). RNA editing may modify the structure, stability, and processing of a transcript. This review focuses on RNA editing in psychiatric, neurological, neurodegenerative (NDs), and autoimmune brain disorders in humans and rodent models. We discuss targeted studies that focus on RNA editing in specific neuron-enriched transcripts with well-established functions in neuronal activity, and transcriptome-wide studies, enabled by recent technological advances. We provide comparative editome analyses between human disease and corresponding animal models. Data suggest RNA editing to be an emerging mechanism in disease development, displaying common and disease-specific patterns. Commonly edited RNAs represent potential disease-associated targets for therapeutic and diagnostic values. Currently available data are primarily descriptive, calling for additional research to expand global editing profiles and to provide disease mechanistic insights. The potential use of RNA editing events as disease biomarkers and available tools for RNA editing identification, classification, ranking, and functional characterization that are being developed will enable comprehensive analyses for a better understanding of disease(s) pathogenesis and potential cures.
MeSH term(s)	Adenosine/genetics ; Adenosine/metabolism ; Adenosine Deaminase/genetics ; Adenosine Deaminase/metabolism ; Animals ; Brain/metabolism ; Brain Diseases ; Mammals/metabolism ; Neurodegenerative Diseases/genetics ; RNA ; RNA Editing/genetics
Chemical Substances	RNA (63231-63-0) ; Adenosine Deaminase (EC 3.5.4.4) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2022-03-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review ; Systematic Review
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12030465
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Article ; Online: Profiling Microglia through Single-Cell RNA Sequencing over the Course of Development, Aging, and Disease.

Pettas, Spyros / Karagianni, Korina / Kanata, Eirini / Chatziefstathiou, Athanasia / Christoudia, Nikoletta / Xanthopoulos, Konstantinos / Sklaviadis, Theodoros / Dafou, Dimitra

Cells

2022 Volume 11, Issue 15

Abstract: Microglia are macrophages present in the brain that function as the primary and most important source of immune response in the central nervous system (CNS). Regardless of their multitasking role, our knowledge regarding their molecular heterogeneity is ... ...

Abstract	Microglia are macrophages present in the brain that function as the primary and most important source of immune response in the central nervous system (CNS). Regardless of their multitasking role, our knowledge regarding their molecular heterogeneity is limited; due to technical restrictions, it is only possible to measure gene expression in cell populations, not individual cells, with the results reflecting average mRNA levels. Therefore, recent scientific approaches have focused on single-cell techniques such as single-cell RNA sequencing (scRNAseq), a powerful technique that enables the delineation of transcriptomic cell-to-cell differences, revealing subpopulations with distinct molecular and functional characteristics. Here, we summarize recent studies that focused on transcriptomic microglial subpopulation clustering and classify them into three distinct groups based on age, spatial distribution, and disease. Additionally, we cross-compare populations from different studies to identify expressional and functional overlaps between them.
MeSH term(s)	Central Nervous System ; Microglia/metabolism ; Sequence Analysis, RNA ; Transcriptome/genetics
Language	English
Publishing date	2022-08-02
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11152383
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Article ; Online: Photo-Fenton and TiO

Kanata, Eirini / Paspaltsis, Ioannis / Sotiriadis, Sotiris / Berberidou, Chrysanthi / Tsoumachidou, Sophia / Dafou, Dimitra / Xanthopoulos, Konstantinos / Arsenakis, Minas / Arsenakis, Athanasios / Poulios, Ioannis / Sklaviadis, Theodoros

Molecules (Basel, Switzerland)

2023 Volume 28, Issue 3

Abstract: Photocatalytic inactivation of pathogens in aqueous waste is gaining increasing attention. Several homogeneous and heterogeneous photocatalytic protocols exist using the Fenton's reagent and ... ...

Abstract	Photocatalytic inactivation of pathogens in aqueous waste is gaining increasing attention. Several homogeneous and heterogeneous photocatalytic protocols exist using the Fenton's reagent and TiO
MeSH term(s)	Hydrogen Peroxide ; Titanium/pharmacology ; Catalysis
Chemical Substances	titanium dioxide (15FIX9V2JP) ; Hydrogen Peroxide (BBX060AN9V) ; Titanium (D1JT611TNE)
Language	English
Publishing date	2023-01-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28031199
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Article: Recommendations for detection, validation, and evaluation of RNA editing events in cardiovascular and neurological/neurodegenerative diseases.

Karagianni, Korina / Bibi, Alessia / Madé, Alisia / Acharya, Shubhra / Parkkonen, Mikko / Barbalata, Teodora / Srivastava, Prashant K / de Gonzalo-Calvo, David / Emanueli, Constanza / Martelli, Fabio / Devaux, Yvan / Dafou, Dimitra / Nossent, A Yaël

Molecular therapy. Nucleic acids

2023 Volume 35, Issue 1, Page(s) 102085

Abstract: RNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the ...

Abstract	RNA editing, a common and potentially highly functional form of RNA modification, encompasses two different RNA modifications, namely adenosine to inosine (A-to-I) and cytidine to uridine (C-to-U) editing. As inosines are interpreted as guanosines by the cellular machinery, both A-to-I and C-to-U editing change the nucleotide sequence of the RNA. Editing events in coding sequences have the potential to change the amino acid sequence of proteins, whereas editing events in noncoding RNAs can, for example, affect microRNA target binding. With advancing RNA sequencing technology, more RNA editing events are being discovered, studied, and reported. However, RNA editing events are still often overlooked or discarded as sequence read quality defects. With this position paper, we aim to provide guidelines and recommendations for the detection, validation, and follow-up experiments to study RNA editing, taking examples from the fields of cardiovascular and brain disease. We discuss all steps, from sample collection, storage, and preparation, to different strategies for RNA sequencing and editing-sensitive data analysis strategies, to validation and follow-up experiments, as well as potential pitfalls and gaps in the available technologies. This paper may be used as an experimental guideline for RNA editing studies in any disease context.
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2662631-7
ISSN	2162-2531
ISSN	2162-2531
DOI	10.1016/j.omtn.2023.102085
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