Ribosome-Directed Therapies in Cancer

Temaj, Gazmend; Chichiarelli, Silvia; Eufemi, Margherita; Altieri, Fabio; Hadziselimovic, Rifat; Farooqi, Ammad Ahmad; Yaylım, İlhan; Saso, Luciano

doi:10.3390/biomedicines10092088

Cited by 23 publications

(11 citation statements)

References 217 publications

(256 reference statements)

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“…8A-D ). As revealed by ORO staining, Etoposide, a classic inhibitor of DNA unwinding, as well as Acivicin and Streptonigrin, two inhibitors of ribosome biogenesis and assembly (38, 39), significantly impeded 3T3- L1 differentiation when administered during the first 48h or during the full process of differentiation ( Sup. Fig.…”

Section: Resultsmentioning

confidence: 99%

14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation

Rial,

You,

Vivoli

et al. 2024

Preprint

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We previously established the scaffold protein 14-3-3ζ as a critical regulator of adipogenesis and adiposity, but the temporal specificity of its action during adipocyte differentiation remains unclear. To decipher if 14-3-3ζ exerts its regulatory functions on mature adipocytes or on adipose precursor cells (APCs), we generated Adipoq14-3-3ζKO and Pdgfra14-3-3ζKO mouse models. Our findings revealed a pivotal role for 14-3-3ζ in APC differentiation in a sex-dependent manner, whereby male and female Pdgfra14-3-3ζKO mice display impaired or potentiated weight gain, respectively, as well as fat mass. To better understand how 14-3-3ζ regulates the adipogenic transcriptional program in APCs, CRISPR-Cas9 was used to generate TAP-tagged 14-3-3ζ-expressing 3T3-L1 preadipocytes. Using these cells, we examined if the 14-3-3ζ nuclear interactome is enriched with adipogenic regulators during differentiation. Regulators of chromatin remodeling, such as DNMT1 and HDAC1, were enriched in the nuclear interactome of 14-3-3ζ, and their activities were impacted upon 14-3-3ζ depletion. The interactions between 14-3-3ζ and chromatin-modifying enzymes suggested that 14-3-3ζ may control chromatin remodeling during adipogenesis, and this was confirmed by ATAC-seq, which revealed that 14-3-3ζ depletion impacted the accessibility of up to 1,244 chromatin regions corresponding in part to adipogenic genes, promoters, and enhancers during the initial stages of adipogenesis. Moreover, 14-3-3ζ-dependent chromatin accessibility was found to directly correlate with the expression of key adipogenic genes. Altogether, our study establishes 14-3-3ζ as a crucial epigenetic regulator of adipogenesis and highlights the usefulness of deciphering the nuclear 14-3-3ζ interactome to identify novel pro-adipogenic factors and pathways.

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Section: Resultsmentioning

confidence: 99%

14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation

Rial,

You,

Vivoli

et al. 2024

Preprint

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“…And ribosome biogenesis hyperactivation addiction in cancer cells is clear, by illustrating its numerous molecules as cancer treatments through impairing ribosome production [24] .In normal cells,ribosomes are involved in proliferating by synthesizing proteins, but in cancer cells,ribosomes are needed according to metabolic requirements. And what's more, previous study has reported that cancer cells express about nearly 10,000 different proteins [25] . Ribosome biogenesis can be a target in cancer cells because of three main reasons, rstly in certain cancer types and its cell populations,this process is highly active and essential,secondly several chemotherapy drugs have been already proven to exert their some pharmacological effects partly,through impairing ribosome biogenesis, and last but not the least blocking ribosome biogenesis can lead in a lot of cases to the activation of p53 [26] .…”

Section: Discussionmentioning

confidence: 98%

The Identification of Hub Genes Associated with Pure Ground Glass Nodules Using Weighted Gene Co-Expression Network Analysis

Cheng,

Song

2023

Preprint

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Background Whether there are invasive components in pure ground glass nodules(pGGNs) in the lungs is still a huge challenge to forecast. The objective of our study is to investigate and identify the potential biomarker genes for pure ground glass nodule(pGGN) based on the method of bioinformatics analysis. Methods To investigate differentially expressed genes (DEGs), firstly we used the data obtained from the gene expression omnibus (GEO) database.Next Weighted gene co-expression network analysis (WGCNA) was used to investigate the co-expression network of DEGs and seven key modules were found. We chose the black key module as the key one in correlation with pGGN. SangerBox software was used for analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Then we used STRING to create a protein-protein interaction (PPI) network, and the chosen module genes were analyzed by Cytoscape software. At last the polymerase chain reaction (PCR) was used to evaluate the value of these hub genes in pGGN patients’ tumor tissues compared to controls. Results There are a total of 4475 DEGs were screened out from GSE193725, then 225 DEGs were identified in black key module. And these DEGs were found to be enriched for various functions and pathways, such as extracellular exosome, vesicle, protein processing in endoplasmic reticulum, metabolic pathways, ribosome, and so on. Among these DEGs, 6 overlapped hub genes with high degrees of stress method were selected. These hub genes include RPL4, RPL8, RPLP0, RPS16, RPS2 and CCT3.And relative expression levels of CCT3 and RPL8 mRNA were both regulated in pGGN patients’ tumor tissues compared to controls. To summarize, the determined DEGs, pathways, modules, and overlapped hub genes can throw light on the potential molecular mechanisms of pGGN.

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“…Consequent functional enrichment analysis of these four modules unveiled connections to pathways related to esophageal cancer progression, multiple research studies corroborate with these findings. Specifically, Module 1 has shown significant connections to translational elongation and ribosomal functions ( Figure 4A ; Temaj et al, 2022 ), Module 2 is linked to histone function, activation of matrix metalloproteinases, and interferon signaling ( Figure 4B ; Jiao et al, 2014 ; Mittal et al, 2016 ; Ozkan and Bakar-Ates, 2020 ), Module 3 is primarily associated with mRNA regulation ( Figure 4C ; Teng et al, 2022 ), and Module 4 is chiefly related to chemokine activity ( Figure 4D ; Nicolau-Neto et al, 2018 ). Each of these modules seems to have a unique role in the progression of esophageal cancer.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan

Sharip,

Rakhimova,

Molkenov

et al. 2024

Front. Genet.

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Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in Central Asia, often diagnosed at advanced stages. Understanding population-specific patterns of ESCC is crucial for tailored treatments. This study aimed to unravel ESCC’s genetic basis in Kazakhstani patients and identify potential biomarkers for early diagnosis and targeted therapies. ESCC patients from Kazakhstan were studied. We analyzed histological subtypes and conducted in-depth transcriptome sequencing. Differential gene expression analysis was performed, and significantly dysregulated pathways were identified using KEGG pathway analysis (p-value < 0.05). Protein-protein interaction networks were constructed to elucidate key modules and their functions. Among Kazakhstani patients, ESCC with moderate dysplasia was the most prevalent subtype. We identified 42 significantly upregulated and two significantly downregulated KEGG pathways, highlighting molecular mechanisms driving ESCC pathogenesis. Immune-related pathways, such as viral protein interaction with cytokines, rheumatoid arthritis, and oxidative phosphorylation, were elevated, suggesting immune system involvement. Conversely, downregulated pathways were associated with extracellular matrix degradation, crucial in cancer invasion and metastasis. Protein-protein interaction network analysis revealed four distinct modules with specific functions, implicating pathways in esophageal cancer development. High-throughput transcriptome sequencing elucidated critical molecular pathways underlying esophageal carcinogenesis in Kazakhstani patients. Insights into dysregulated pathways offer potential for early diagnosis and precision treatment strategies for ESCC. Understanding population-specific patterns is essential for personalized approaches to ESCC management.

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Ribosome-Directed Therapies in Cancer

Cited by 23 publications

References 217 publications

14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation

14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation

The Identification of Hub Genes Associated with Pure Ground Glass Nodules Using Weighted Gene Co-Expression Network Analysis

Transcriptome profiling and analysis of patients with esophageal squamous cell carcinoma from Kazakhstan

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