MDM2 inhibitors-mediated disruption of mitochondrial metabolism: A novel therapeutic strategy for retinoblastoma

Romani, Arianna; Zauli, Enrico; Zauli, Giorgio; Al-Mesfer, Saleh; Al-Swailem, Samar A; Voltan, Rebecca

doi:10.3389/fonc.2022.1000677

Cited by 5 publications

(5 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, SPRY2 (Sprouty RTK Signaling Antagonist 2) encodes a protein that belongs to the Sprouty family [ 34 – 37 ]. Outcomes from GSEA were enriched for p53 SIGNALING PATHWAY and SPLICEOSOME, in agreement with previous findings, indicating that the gene plays an important role in RB initiation and development [ 38 , 39 ].…”

Section: Discussionsupporting

confidence: 90%

Retinoblastoma gene expression profiling based on bioinformatics analysis

Murai

et al. 2023

BMC Med Genomics

View full text Add to dashboard Cite

Background Retinoblastoma (RB) is frequently occurring malignant tumors that originate in the retina, and their exact cause and development mechanisms are yet to be fully comprehended. In this study, we identified possible biomarkers for RB and delved into the molecular mechanics linked with such markers. Methods In this study GSE110811 and GSE24673 were analyzed. Weighted gene co-expression network analysis (WGCNA) was applied to screen modules and genes associated with RB. By overlapping RB-related module genes with differentially expressed genes (DEGs) between RB and control samples, differentially expressed retinoblastoma genes (DERBGs) were acquired. A gene ontology (GO) enrichment analysis and a kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were conducted to explore the functions of these DERBGs. To study the protein interactions of DERBGs, a protein–protein interaction (PPI) network was constructed. Hub DERBGs were screened using the least absolute shrinkage and selection operator (LASSO) regression analysis, as well as the random forest (RF) algorithm. Additionally, the diagnostic performance of RF and LASSO methods was evaluated using receiver operating characteristic (ROC) curves and single-gene gene set enrichment analysis (GSEA) was conducted to explore the potential molecular mechanisms involved with these Hub DERBGs. In addition, the competing endogenous RNA (ceRNA) regulatory network of Hub DERBGs was constructed. Result About 133 DERBGs were found to be associated with RB. GO and KEGG enrichment analyses revealed that the important pathways of these DERBGs. Furthermore, the PPI network revealed 82 DERBGs interacting with each other. By RF and LASSO methods, PDE8B, ESRRB, and SPRY2 were identified as Hub DERBGs in patients with RB. From the expression assessment of Hub DERBGs, it was found that the levels of expression of PDE8B, ESRRB, and SPRY2 were significantly decreased in the tissues of RB tumors. Secondly, single-gene GSEA revealed a connection between these 3 Hub DERBGs and oocyte meiosis, cell cycle, and spliceosome. Finally, the ceRNA regulatory network revealed that hsa-miR-342-3p, hsa-miR-146b-5p, hsa-miR-665, and hsa-miR-188-5p may play a central role in the disease. Conclusion Hub DERBGs may provide new insight into RB diagnosis and treatment based on the understanding of disease pathogenesis.

show abstract

Section: Discussionsupporting

confidence: 90%

Retinoblastoma gene expression profiling based on bioinformatics analysis

Murai

et al. 2023

BMC Med Genomics

View full text Add to dashboard Cite

show abstract

“…Apoptosis refers to the natural process during which cells are destroyed. Therefore, nutlin-3a treatment stimulates increased production of p53, which is a tumor suppressor, and translocates this protein to the nucleus to regulate cell growth by inducing apoptosis [ 60 ]. The induced cell death inhibits the rapid cell differentiation of retinal cells, reducing retinoblastoma.…”

Section: Clinical Applications and Outcomesmentioning

confidence: 99%

Genetic Risk Factors and Clinical Outcomes in Childhood Eye Cancers: A Review

Hameed,

Yu,

Almadani

et al. 2024

Genes

Self Cite

View full text Add to dashboard Cite

Childhood eye cancers, although rare, present substantial health challenges, affecting the pediatric population with a remarkable impact on their lives and families. This comprehensive review provides insights into the various types of ocular tumors, primarily focusing on malignant eye tumors, their genetic predispositions, and advancements in managing these conditions. Understanding the genetic risk factors is crucial for early detection, risk assessment, and the development of targeted therapies. This review discusses genome-wide association (GWAS) and next-generation sequencing (NGS) studies to find common and rare genetic variants. Furthermore, it also explores the outcomes and implications of these genetic discoveries in treating pediatric ocular cancer. These findings underscore the significance of genetic research in guiding early interventions and improving outcomes in children with ocular cancers.

show abstract

“…Along with the nuclear migration and the regulation of the cell cycle, p53 may also promote the intrinsic apoptotic pathway, also known as mitochondrial apoptosis [63,74]. The intrinsic apoptotic pathway is driven by the Bcl-2 family of proteins, the activation of which depends on the p53 activity.…”

Section: The Role Of P53 In Tissue and Ocular Homeostasismentioning

confidence: 99%

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies

Casciano

Zauli

Busin

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

The pivotal role of p53 in the regulation of a vast array of cellular functions has been the subject of extensive research. The biological activity of p53 is not strictly limited to cell cycle arrest but also includes the regulation of homeostasis, DNA repair, apoptosis, and senescence. Thus, mutations in the p53 gene with loss of function represent one of the major mechanisms for cancer development. As expected, due to its key role, p53 is expressed throughout the human body including the eye. Specifically, altered p53 signaling pathways have been implicated in the development of conjunctival and corneal tumors, retinoblastoma, uveal melanoma, and intraocular melanoma. As non-selective cancer chemotherapies as well as ionizing radiation can be associated with either poor efficacy or dose-limiting toxicities in the eye, reconstitution of the p53 signaling pathway currently represents an attractive target for cancer therapy. The present review discusses the role of p53 in the pathogenesis of these ocular tumors and outlines the various pharmacological activators of p53 that are currently under investigation for the treatment of ocular malignancies.

show abstract

MDM2 inhibitors-mediated disruption of mitochondrial metabolism: A novel therapeutic strategy for retinoblastoma

Cited by 5 publications

References 80 publications

Retinoblastoma gene expression profiling based on bioinformatics analysis

Retinoblastoma gene expression profiling based on bioinformatics analysis

Genetic Risk Factors and Clinical Outcomes in Childhood Eye Cancers: A Review

State of the Art of Pharmacological Activators of p53 in Ocular Malignancies

Contact Info

Product

Resources

About