A pan-cancer single-cell RNA-seq atlas of intratumoral B cells

Cancer Cell, Journal Year: 2024, Volume and Issue: 42(10), P. 1784 - 1797.e4

Published: Oct. 1, 2024

Language: Английский

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Sequential MALDI-HiPLEX-IHC and Untargeted Spatial Proteomics Mass Spectrometry Imaging to Detect Proteomic Alterations Associated with Tumour Infiltrating Lymphocytes

Journal of Proteome Research, Journal Year: 2025, Volume and Issue: 24(2), P. 871 - 880

Published: Jan. 3, 2025

MALDI-HiPLEX-IHC mass spectrometry imaging (MSI) represents a newly established workflow to map tens of antibodies linked photocleavable tags (PC-MTs), which report the distribution antigens in formalin-fixed paraffin-embedded (FFPE) tissue sections. While this highly multiplexed approach has previously been integrated with untargeted methods, possibility mapping target cell and performing bottom-up spatial proteomics on same section yet be explored. This proof-of-concept study presents novel combining analyze single FFPE section, using clinical clear renal carcinoma (ccRCC) as model. Workflow implementation highlighted need for an additional antigen retrieval step following antibody staining aid detachment enhance tryptic digestion. Moreover, enabled stratification histologically similar tumor cores grade based varying lymphocyte populations, particularly T regulatory cells. Finally, integration revealed proteomic alterations associated these infiltration patterns. These findings demonstrate potential characterize molecular environment tumor-infiltrating lymphocytes, offering insights into impact immune cells within microenvironment.

Language: Английский

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Ribosome Biogenesis, Altered Metabolism and Ribotoxic Stress Response in Pancreatic Ductal Adenocarcinoma Tumor Microenvironment

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217484 - 217484

Published: Jan. 1, 2025

Language: Английский

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Small nucleolar RNAs: the hidden precursors of cancer ribosomes.

PubMed, Journal Year: 2025, Volume and Issue: 380(1921), P. 20230376 - 20230376

Published: March 6, 2025

Ribosomes are heterogeneous in terms of their constituent proteins, structural RNAs and ribosomal RNA (rRNA) modifications, resulting diverse potential translatomes. rRNA guided by small nucleolar (snoRNAs), enable fine-tuning ribosome function translation profiles. Recent studies have begun linking dysregulation snoRNAs, via to tumourigenesis. Deciphering the specific contributions individual modifications cancer hallmarks identifying snoRNAs with oncogenic could lead novel therapeutic strategies. These strategies might target or exploit dependence cells on modification sites, potentially disrupting aberrant programs hindering tumour growth. This review discusses current evidence challenges changes snoRNA expression biology.This article is part discussion meeting issue 'Ribosome diversity its impact protein synthesis, development disease'.

Language: Английский

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SMYD5 is a ribosomal methyltransferase that catalyzes RPL40 lysine methylation to enhance translation output and promote hepatocellular carcinoma

Cell Research, Journal Year: 2024, Volume and Issue: 34(9), P. 648 - 660

Published: Aug. 5, 2024

Abstract While lysine methylation is well-known for regulating gene expression transcriptionally, its implications in translation have been largely uncharted. Trimethylation at 22 (K22me3) on RPL40, a core ribosomal protein located the GTPase activation center, was first reported 27 years ago. Yet, methyltransferase and role remain unexplored. Here, we report that SMYD5 has robust vitro activity toward RPL40 K22 primarily catalyzes K22me3 cells. The loss of leads to reduced output disturbed elongation as evidenced by increased ribosome collisions. are upregulated hepatocellular carcinoma (HCC) negatively correlated with patient prognosis. Depleting renders HCC cells hypersensitive mTOR inhibition both 2D 3D cultures. Additionally, markedly inhibits development growth genetically engineered mouse patient-derived xenograft (PDX) models, inhibitory effect PDX model further enhanced concurrent suppression. Our findings reveal novel axis highlight therapeutic potential targeting HCC, particularly inhibition. This work also conceptually broadens understanding methylation, extending significance from transcriptional regulation translational control.

Language: Английский

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Hypermethylation at 45S rDNA promoter in cancers

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0311085 - e0311085

Published: Jan. 7, 2025

The ribosomal genes ( rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation ribosome biogenesis has been recognized as a hallmark feature, thus, reduced methylation promoter thought support conformational changes chromatin accessibility subsequent increase in transcription. However, an state hypermethylation can be protective mechanism teetering on brink threshold where cells rarely successfully proliferate. Hence, clarifying hypo- or will unravel its additional functions, including organization genome architecture regulation gene expression, response growth signaling, stressors, carcinogenesis. Using bisulfite-based quantitative real-time methylation-specific PCR (qMSP) method after ensuring unbiased amplification complete bisulfite conversion minuscule amount 1 ng, we established that was significantly hypermethylated 107 breast, 65 lung, 135 colon tumour tissue samples (46.81%, 51.02% 96.60%, respectively) compared with their corresponding adjacent normal (26.84%, 38.26% 77.52%, respectively; p < 0.0001). An excessive input μg resulted double-stranded remaining unconverted even conversion, hence dramatic drop single-stranded strictly required leading underestimation methylation, words, faulty hypomethylation status promoter. Our results line hypothesis natural pathway protecting repeats extremely sensitive damage cells.

Language: Английский

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From Flies to Humans: Conserved Roles of CEBPZ, NOC2L, and NOC3L in rRNA Processing and Tumorigenesis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Abstract NOC1, NOC2, and NOC3 are conserved nucleolar proteins essential for regulating ribosomal RNA (rRNA) maturation, a process critical cellular homeostasis. in Drosophila yeast, enhances activity to sustain rRNA processing, whereas its depletion leads impaired polysome formation, reduced protein synthesis, apoptosis. These genes have vertebrate homologs called CEBPZ, NOC2L, NOC3l. In this study, we demonstrated that the RNA-regulatory functions of CEBPZ vertebrates, showed accumulation 45S-pre rRNA, with consequent reduction synthesis. Gene Ontology bioinformatic analyses NOC3L tumors highlight significant correlation between their processes regulate 60S maturation. Comparative analysis expression tumor databases revealed exhibit contrasting patterns across types. This dual role suggests overexpression promotes growth, may exert tumor-suppressive effects, uncovering unexpected regulatory exerted by these cancer.

Language: Английский

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lncRNAs: the unexpected link between protein synthesis and cancer adaptation

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 31, 2025

Cancer progression relies on the ability of cells to adapt challenging environments overcoming stresses and growth constraints. Such adaptation is a multifactorial process that depends rapid reorganization many basic cellular mechanisms. Protein synthesis often dysregulated in cancer, translational reprogramming emerging as driving force cancer adaptive plasticity. Long non-coding RNAs (lncRNAs) represent main product genome transcription. They outnumber mRNAs by an order magnitude their expression regulated extremely specific manner depending context, space time. This heterogeneity functional allows lncRNAs act context-specific, fine-tuning controllers gene expression. Multiple recent evidence underlines how, besides consolidated role transcription, are major players translation control. Their capacity establish multiple highly dynamic interactions with proteins other transcripts makes these molecules able play central across all phases protein synthesis. Even if through myriad different mechanisms, action dual. On one hand, modulating overall speed, participate metabolic under stress conditions. prioritizing they help maintain high levels essential oncogenes. In this review, we aim discuss most relevant regarding involvement regulation how function may affect plasticity resistance stress. We also expect provide first collective perspectives way modulate beyond

Language: Английский

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Unlocking RNA mysteries: Predicting subcellular localizations with AI

Molecular Therapy — Nucleic Acids, Journal Year: 2025, Volume and Issue: 36(1), P. 102481 - 102481

Published: Feb. 21, 2025

Language: Английский

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Ribosome-directed cancer therapies: the tip of the iceberg?

Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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