Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.Peer reviewe

Deciphering the Role of microRNA Mediated Regulation of Coronin 1C in Glioblastoma Development and Metastasis

© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Glioblastoma multiforme (GBM) is a highly heterogenic and malignant brain tumour with a median survival of 15 months. The initial identification of primary glioblastomas is often challenging. Coronin 1C (CORO1C) is a key player in actin rearrangement and cofilin dynamics, as well as enhancing the processes of neurite overgrowth and migration of brain tumour cells. Different bioinformatic databases were accessed to measure CORO1C expression at the mRNA and protein level in normal and malignant brains. CORO1C expression was observed in brain regions which have retained high synaptic plasticity and myelination properties. CORO1C was also expressed mainly within the hippocampus formation, including the Cornu Ammonis (CA) fields: CA1-CA4. Higher expression was also noticed in paediatric GBM in comparison to their adult counterparts. Pediatric cell populations were observed to have an increased log2 expression of CORO1C. Furthermore, 62 miRNAs were found to target the CORO1C gene. Of these, hsa-miR-34a-5p, hsa-miR-512-3p, hsa-miR-136-5p, hsa-miR-206, hsa-miR-128-3p, and hsa-miR-21-5p have shown to act as tumour suppressors or oncomiRs in different neoplasms, including GBM. The elevated expression of CORO1C in high grade metastatic brain malignancies, including GBM, suggests that this protein could have a clinical utility as a biomarker linked to an unfavorable outcome.Peer reviewe

Dysregulated placental microRNAs in Early and Late onset Preeclampsia

Copyright © 2017. Published by Elsevier Ltd.INTRODUCTION: To determine the miRNA expression profile in placentas complicated by Preeclampsia (PE) and compare it to uncomplicated pregnancies. METHODS: Sixteen placentas from women with PE, [11 with early onset PE (EOPE) and 5 with late onset PE (LOPE)], as well as 8 placentas from uncomplicated pregnancies were analyzed using miRNA microarrays. For statistical analyses the MATLAB® simulation environment was applied. The over-expression of miR-518a-5p was verified using Quantitative Real-Time Polymerase Chain Reaction. RESULTS: Forty four miRNAs were found dysregulated in PE complicated placentas. Statistical analysis revealed that miR-431, miR-518a-5p and miR-124* were over-expressed in EOPE complicated placentas as compared to controls, whereas miR-544 and miR-3942 were down-regulated in EOPE. When comparing the miRNA expression profile in cases with PE and PE-growth restricted fetuses (FGR), miR-431 and miR-518a-5p were found over-expressed in pregnancies complicated by FGR. DISCUSSION: Since specific miRNAs can differentiate EOPE and LOPE from uncomplicated placentas, they may be considered as putative PE-specific biomarkers. MiR-518a-5p emerged as a potential diagnostic indicator for EOPE cases as well as for PE-FGR complicated placentas, indicating a potential link to the severity of the disease.Peer reviewe

MYCN in Neuroblastoma: “Old Wine into New Wineskins”

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)MYCN Proto-Oncogene, BHLH Transcription Factor (MYCN) has been one of the most studied genes in neuroblastoma. It is known for its oncogenetic mechanisms, as well as its role in the prognosis of the disease and it is considered one of the prominent targets for neuroblastoma therapy. In the present work, we attempted to review the literature, on the relation between MYCN and neuroblastoma from all possible mechanistic sites. We have searched the literature for the role of MYCN in neuroblastoma based on the following topics: the references of MYCN in the literature, the gene’s anatomy, along with its transcripts, the protein’s anatomy, the epigenetic mechanisms regulating MYCN expression and function, as well as MYCN amplification. MYCN plays a significant role in neuroblastoma biology. Its functions and properties range from the forming of G-quadraplexes, to the interaction with miRNAs, as well as the regulation of gene methylation and histone acetylation and deacetylation. Although MYCN is one of the most primary genes studied in neuroblastoma, there is still a lot to be learned. Our knowledge on the exact mechanisms of MYCN amplification, etiology and potential interventions is still limited. The knowledge on the molecular mechanisms of MYCN in neuroblastoma, could have potential prognostic and therapeutic advantages.Peer reviewe

Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology

© 2024 The Author(s). Published by Cambridge University Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.Peer reviewe

Circular RNAs: New layer of complexity evading breast cancer heterogeneity

© 2022 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Advances in high-throughput sequencing techniques and bioinformatic analysis have refuted the "junk" RNA hypothesis that was claimed against non-coding RNAs (ncRNAs). Circular RNAs (circRNAs); a class of single-stranded covalently closed loop RNA molecules have recently emerged as stable epigenetic regulators. Although the exact regulatory role of circRNAs is still to be clarified, it has been proven that circRNAs could exert their functions by interacting with other ncRNAs or proteins in their own physiologically authentic environment, regulating multiple cellular signaling pathways and other classes of ncRNAs. CircRNAs have also been reported to exhibit a tissue-specific expression and have been associated with the malignant transformation process of several hematological and solid malignancies. Along this line of reasoning, this review aims to highlight the importance of circRNAs in Breast Cancer (BC), which is ranked as the most prevalent malignancy among females. Notwithstanding the substantial efforts to develop a suitable anticancer therapeutic regimen against the heterogenous BC, inter- and intra-tumoral heterogeneity have resulted in an arduous challenge for drug development research, which in turn necessitates the investigation of other markers to be therapeutically targeted. Herein, the potential of circRNAs as possible diagnostic and prognostic biomarkers have been highlighted together with their possible application as novel therapeutic targets.Peer reviewe

MicroRNA Biomarkers in Primary Brain Malignancies

Despite the concerted efforts within the management of brain malignancies over the past few decades, primary brain cancers remain an obscure challenge with unfavourable outcomes for the patients. Glioblastomas (GBM) and medulloblastomas afford the most prevalent brain tumours and account for markedly high mortality rates within affected patients. The unmet clinical requirements for an early diagnostic biomarker and effective treatment have shed light onto microRNAs (miRNAs). These are small, endogenous noncoding RNAs involved in a wide spectrum of biological processes, such as post-translational modification, tumorigenesis, angiogenesis, invasiveness, and apoptosis. Increased expression of miR-21 has been shown to have devastating effects upon patients with brain tumours, and it could be used as a diagnostic biomarker and an early relapse indicator. miRNAs such as miR-128a, miR-34a, miR-7 and miR-1253 have demonstrated tumour suppressive properties and could serve as putative therapeutic agents. MiRNA signatures, such as miR-21 and miR-10b could be incorporated as potential prognostic indicators for advanced and metastatic brain malignancies, whereas miR-221/222 cluster has a therapeutic potential to sensitise cancerous cells towards radiotherapy. Herein, we summarised current knowledge on how miRNAs with significant role in glioblastomas and medulloblastomas specifically can be effectively used as promising brain cancer diagnostics, prognostics, and therapeutics

Analysis of SIGLEC12 expression, IMMUNOMODULATION and prognostic value in RENAL cancer using multiomic databases

© 2024 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Siglecs belong to a family of immune regulatory receptors predominantly found on hematopoietic cells. They interact with Sia, resulting in the activation or inhibition of the immune response. Previous reports have suggested that the SIGLEC12 gene, which encodes the Siglec-XII protein, is expressed in the epithelial tissues and upregulated in carcinomas. However, studies deciphering the role of Siglec-XII in renal cancer (RC) are still unavailable, and here we provide insights on this question. We conducted expression analysis using the Human Protein Atlas and UALCAN databases. The impact of SIGLEC12 on RC prognosis was determined using the KM plotter, and an assessment of immune infiltration with SIGLEC12 was performed using the TIMER database. GSEA was conducted to identify the pathways affected by SIGLEC12. Finally, using GeneMania, we identified Siglec-XII interacting proteins. Our findings indicated that macrophages express SIGLEC12 in the kidney. Furthermore, we hypothesize that Siglec-XII expression might be involved in the increase of primary RC, but this effect may not be dependent on the age of the patient. In the tumour microenvironment, oncogenic pathways appeared to be upregulated by SIGLEC12. Similarly, our analysis suggested that SIGLEC12-related kidney renal papillary cell carcinomas may be more suitable for targeted immunotherapy, such as CTLA-4 and PD-1/PD-L1 inhibitors. These preliminary results suggested that high expression of SIGLEC12 is associated with poor prognosis for RC. Future studies to assess its clinical utility are necessitated.Peer reviewe

Differential and Common Signatures of miRNA Expression and Methylation in Childhood Central Nervous System Malignancies: An Experimental and Computational Approach

© 2021 by the authors. This is an open access article distributed under the Creative Commons Attribution License. https://creativecommons.org/licenses/by/4.0/Epigenetic modifications are considered of utmost significance for tumor ontogenesis and progression. Especially, it has been found that miRNA expression, as well as DNA methylation plays a significant role in central nervous system tumors during childhood. A total of 49 resected brain tumors from children were used for further analysis. DNA methylation was identified with methylation-specific MLPA and, in particular, for the tumor suppressor genes CASP8, RASSF1, MGMT, MSH6, GATA5, ATM1, TP53, and CADM1. miRNAs were identified with microarray screening, as well as selected samples, were tested for their mRNA expression levels. CASP8, RASSF1 were the most frequently methylated genes in all tumor samples. Simultaneous methylation of genes manifested significant results with respect to tumor staging, tumor type, and the differentiation of tumor and control samples. There was no significant dependence observed with the methylation of one gene promoter, rather with the simultaneous presence of all detected methylated genes’ promoters. miRNA expression was found to be correlated to gene methylation. Epigenetic regulation appears to be of major importance in tumor progression and pathophysiology, making it an imperative field of study.Peer reviewe