The ion channels and transporters gene expression profile indicates a shift in excitability and metabolisms during malignant progression of Follicular Lymphoma

Magi, Alberto; Masselli, Marika; Sala, Cesare; Guerriero, Angela; Laise, Pasquale; Puccini, Benedetta; Rigacci, Luigi; Breschi, C; Crociani, Olivia; Pillozzi, Serena; Arcangeli, Annarosa

doi:10.1038/s41598-019-44661-x

Cited by 21 publications

(17 citation statements)

References 44 publications

(53 reference statements)

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“…The mitochondrial remodelling in KRAS mutated-BRAF wild-type CRC agree with Warburg's hypothesis, suggesting that the scenario might be different to that observed in other tumours, as in the case of the relevant role of OXPHOS in lymphomas [46].…”

Section: Discussionsupporting

confidence: 77%

A Transcriptomic Approach Reveals Selective Ribosomal Remodelling in the Tumour Versus the Stromal Compartment of Metastatic Colorectal Cancer

Lastraioli

Costanzo

Sala

et al. 2021

Cancers

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Because of its high incidence and poor prognosis, colorectal cancer (CRC) represents an important health issue in several countries. As with other carcinomas, the so-called tumour microenvironment (TME) has been shown to play key roles in CRC progression and related therapeutical outcomes, even though a deeper understanding of the underlying molecular mechanisms is needed to devise new treatment strategies. For some years now, omics technologies and consolidated bioinformatics pipelines have allowed scientists to access large amounts of biologically relevant information, even when starting from small tissue samples; thus, in order to shed new light upon the role of the TME in CRC, we compared the gene expression profiles of 6 independent tumour tissues (all progressed towards metastatic disease) to the expression profile of the surrounding stromata. To do this, paraffin-embedded whole tissues were first microdissected to obtain samples enriched with tumour and stromal cells, respectively. Afterwards, RNA was extracted and analysed using a microarray-based approach. A thorough bioinformatics analysis was then carried out to identify transcripts differentially expressed between the two groups and possibly enriched functional terms. Overall, 193 genes were found to be significantly downregulated in tumours compared to the paired stromata. The functional analysis of the downregulated gene list revealed three principal macro areas of interest: the extracellular matrix, cell migration, and angiogenesis. Conversely, among the upregulated genes, the main alterations detected by the functional annotation were related to the ribosomal proteins (rProteins) of both the large (60S) and small (40S) subunits of the cytosolic ribosomes. Subsequent gene set enrichment analysis (GSEA) confirmed the massive overexpression of most cytosolic—but not mitochondrial—ribosome rProteins.

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Section: Discussionsupporting

confidence: 77%

A Transcriptomic Approach Reveals Selective Ribosomal Remodelling in the Tumour Versus the Stromal Compartment of Metastatic Colorectal Cancer

Lastraioli

Costanzo

Sala

et al. 2021

Cancers

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“…4g). Some of the genes associated with these 16 sites included PLEKHA7, AP1M2, ATP9A, and ARVCF known to be downregulated in breast and prostate cancer (data not shown), as well as other cancers [30][31][32][33][34][35].…”

Section: Discussionmentioning

confidence: 99%

CTCF loss mediates unique DNA hypermethylation landscapes in human cancers

et al. 2020

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Background: The chromatin insulator CCCTC-binding factor (CTCF) displays tissue-specific DNA binding sites that regulate transcription and chromatin organization. Despite evidence linking CTCF to the protection of epigenetic states through barrier insulation, the impact of CTCF loss on genome-wide DNA methylation sites in human cancer remains undefined. Results: Here, we demonstrate that prostate and breast cancers within The Cancer Genome Atlas (TCGA) exhibit frequent copy number loss of CTCF and that this loss is associated with increased DNA methylation events that occur preferentially at CTCF binding sites. CTCF sites differ among tumor types and result in tissue-specific methylation patterns with little overlap between breast and prostate cancers. DNA methylation and transcriptome profiling in vitro establish that forced downregulation of CTCF leads to spatially distinct DNA hypermethylation surrounding CTCF binding sites, loss of CTCF binding, and decreased gene expression that is also seen in human tumors. DNA methylation inhibition reverses loss of expression at these CTCF-regulated genes. Conclusion: These findings establish CTCF loss as a major mediator in directing localized DNA hypermethylation events in a tissue-specific fashion and further support its role as a driver of the cancer phenotype.

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“…It has been reported that this process is widely involved with DLBCL metabolic reprogramming 29 . Related ion binding pathways, specifically genes related to ion channels and transporters, as have been associated with DLBCL development and relapse in patients 30 . Other pathways such as neurotrophins and Trk signaling 31 and Fc epsilon receptor signaling 32 have been shown to be involved in DLBCL resistance to therapeutic drugs.…”

Section: Resultsmentioning

confidence: 99%

Identification of Circulating Serum Multi-MicroRNA Signatures in Human DLBCL Models

Beheshti

Stevenson

Vanderburg

et al. 2019

Sci Rep

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There remains a need to identify new sensitive diagnostic and predictive blood-based platforms in lymphoma. We previously discovered a novel circulating microRNA (miRNA) signature in a Smurf2-deficient mouse model that spontaneously develops diffuse large B-cell lymphoma (DLBCL). Herein, we investigated this 10-miRNA signature (miR-15a, let-7c, let-7b, miR-27a, miR-10b, miR-18a, miR-497, miR-130a, miR24, and miR-155) in human lymphoma cell lines, mice engrafted with patient-derived xenografts (PDXs), and DLBCL patient serum samples leveraging systems biology analyses and droplet digital PCR (ddPCR) technology. Overall, 90% of the miRNAs were enriched in PDX DLBCL models and human lymphoma cell lines. Circulating miRNAs from the serum of 86 DLBCL patients were significantly increased compared with healthy controls and had similar patterns to the murine models. Strikingly, miRNAs were identified up to 27-fold higher levels in the serum of PDX-bearing mice and human patients compared with lymphoma cell lysates, suggesting a concentration of these factors over time within sera. Using cut-points from recursive partitioning analysis, we derived a 5-miRNA signature (let-7b, let-7c, miR-18a, miR-24, and miR-15a) with a classification rate of 91% for serum from patients with DLBCL versus normal controls. In addition, higher levels of circulating let-7b miRNA were associated with more advanced stage disease (i.e., III-IV vs. I-II) in DLBCL patients and higher levels of miR-27a and miR-24 were associated with MYC rearrangement. Taken together, circulating multi-miRNAs were readily detectable in pre-clinical cell line and human lymphoma models as well as in DLBCL patients where they appeared to distinguish clinico-pathologic subtypes and disease features.

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The ion channels and transporters gene expression profile indicates a shift in excitability and metabolisms during malignant progression of Follicular Lymphoma

Cited by 21 publications

References 44 publications

A Transcriptomic Approach Reveals Selective Ribosomal Remodelling in the Tumour Versus the Stromal Compartment of Metastatic Colorectal Cancer

A Transcriptomic Approach Reveals Selective Ribosomal Remodelling in the Tumour Versus the Stromal Compartment of Metastatic Colorectal Cancer

CTCF loss mediates unique DNA hypermethylation landscapes in human cancers

Identification of Circulating Serum Multi-MicroRNA Signatures in Human DLBCL Models

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