BMC Cardiovascular Disorders, Год журнала: 2024, Номер 24(1)
Опубликована: Дек. 30, 2024
To screen Myocardial ischemia-reperfusion Injury in mice. adenosine monophate-activatedprotein kinase (AMPK) -related differentially expressed circularRNA (circRNA) MIRI model, Ampk-related circRNA network was drawn to provide possible ideas for the prevention and treatment of MIRI.
Язык: Английский
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Март 15, 2024
Circular RNAs (circRNAs) are covalently closed non-coding lacking the 5' cap and poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses. This study presents immunopeptidomics workflow with a specific focus on generating circRNA-specific protein fasta reference. The main goal this is to streamline process identifying validating leukocyte antigen (HLA) bound peptides originating from circRNAs. We increase analytical stringency our by retaining identified independently two mass spectrometry search engines and/or applying group-specific FDR for canonical-derived circRNA-derived peptides. A subset specifically encoded region spanning back-splice junction (BSJ) validated targeted MS, direct Sanger sequencing respective transcripts. Our identifies 54 unique BSJ-spanning immunopeptidome melanoma lung cancer samples. approach enlarges catalog proteins explored immunotherapy.
Язык: Английский
Процитировано
19
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Сен. 30, 2024
Язык: Английский
Процитировано
12
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Сен. 9, 2024
A major scientific drive is to characterize the protein-coding genome as it provides primary basis for study of human health. But fundamental question remains: what has been missed in prior genomic analyses? Over past decade, translation non-canonical open reading frames (ncORFs) observed across cell types and disease states, with implications proteomics, genomics, clinical science. However, impact ncORFs limited by absence a large-scale understanding their contribution proteome. Here, we report collaborative efforts stakeholders immunopeptidomics, Ribo-seq ORF discovery, gene annotation, produce consensus landscape protein-level evidence ncORFs. We show that at least 25% set 7,264 give rise translated products, yielding over 3,000 peptides pan-proteome analysis encompassing 3.8 billion mass spectra from 95,520 experiments. With these data, developed an annotation framework created public tools researchers through GENCODE PeptideAtlas. This work will provide platform advance ncORF-derived proteins biomedical discovery and, beyond humans, diverse animals plants where are similarly observed.
Язык: Английский
Процитировано
8
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Янв. 9, 2025
Abstract Mitosis is a critical phase of the cell cycle and vulnerable point where cancer cells can be effectively disrupted, leading to death inhibition tumor growth. However, challenges such as drug resistance remain significant in clinical applications. During mitosis, mRNA translation generally downregulated, while non-canonical specific transcripts proceeds. Here, we demonstrate that mitotic redistribute ribosomes toward 5’ untranslated region (5’ UTR) start coding sequence (CDS), enhancing thousands upstream open reading frames (uORFs) overlapping (uoORFs). This induction uORF/uoORF enriches presentation immunopeptides at surface following treatment with inhibitors. Functional assays indicate potential neoepitopes provoke cancer-cell killing by T cells. Altogether, our findings highlight therapeutic targeting uORF/uoORF-derived combination inhibitors enhance immune recognition elimination.
Язык: Английский
Процитировано
0
Frontiers in Immunology, Год журнала: 2025, Номер 16
Опубликована: Янв. 29, 2025
The immunopeptidome, a diverse set of peptides presented by Major Histocompatibility Complex (MHC) molecules, is critical component immune recognition and response. This review article delves into the mechanisms peptide presentation MHC particularly emphasizing roles ncRNA-derived extracellular vesicles (EVs) in shaping immunopeptidome landscape. We explore established emerging insights molecule interactions with peptides, including dynamics loading, transport, influence cellular genetic variations. highlights novel research on non-coding RNA (ncRNA)-derived which challenge conventional views antigen processing role EVs transporting these thereby modulating responses at remote body sites. not only challenges but also opens up new avenues for understanding responses. Furthermore, we discuss implications developing therapeutic strategies, cancer immunotherapy. By conducting comprehensive analysis current literature advanced methodologies immunopeptidomics, this aims to deepen complex interplay between system, offering perspectives potential diagnostic applications. Additionally, provide mechanism enhanced surface highlight pathway their systemic distribution, potentially altering surveillance landscapes.
Язык: Английский
Процитировано
0
Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)
Опубликована: Фев. 19, 2025
In the present era, noncoding RNAs (ncRNAs) have become a subject of considerable scientific interest, with peptides encoded by ncRNAs representing particularly promising avenue investigation. The identification ncRNA-encoded in human cancers is increasing. These regulate cancer progression through multiple molecular mechanisms. Here, we delineate patterns diverse and provide synopsis methodologies employed for that possess capacity to encode these peptides. Furthermore, discuss impacts on biological behavior cells underlying conclusion, describe prospects challenges need be overcome.
Язык: Английский
Процитировано
0
Biomarker Research, Год журнала: 2025, Номер 13(1)
Опубликована: Фев. 20, 2025
Early detection of colorectal cancer (CRC) significantly improves its management and patients' survival. Circular RNAs (circRNAs) are peculiar covalently closed transcripts involved in gene expression modulation whose dysregulation has been extensively reported CRC cells. However, little is known about their alterations the early phases carcinogenesis. In this study, we performed an integrative analysis circRNA profiles RNA-sequencing (RNA-Seq) data 96 cancers, 27 adenomas, matched adjacent mucosa tissues. We also investigated levels cognate linear those regulating RNA-binding proteins (RBPs). Levels circRNA-interacting microRNAs (miRNAs) were explored by integrating small RNA-Seq on same samples. Our results revealed a significant 34 circRNAs (paired adj. p < 0.05), almost exclusively downregulated tumor tissues and, prevalently, disease stages. This downregulation was associated with decreased host genes encoding for RBPs biogenesis, including NOVA1, RBMS3, MBNL1. Guilt-by-association showed that dysregulated correlated increased predicted activity cell proliferation, DNA repair, c-Myc signaling pathways. Functional interactions among circRNAs, RBPs, miRNAs, which supported correlations levels. Findings validated independent cohorts public datasets, circLPAR1(2,3) circLINC00632(5) ddPCR. These support multiple altered regulatory mechanisms may contribute to reduction characterize
Язык: Английский
Процитировано
0
iScience, Год журнала: 2025, Номер 28(4), С. 112183 - 112183
Опубликована: Март 12, 2025
Renal cell carcinoma (RCC), particularly clear RCC (ccRCC), has seen rising incidence and mortality rates. Early detection remains difficult due to nonspecific symptoms, often leading diagnoses at advanced stages unfavorable prognoses. Current treatments, including surgery, targeted therapies, immunotherapies, face limitations such as adverse reactions, drug resistance, immune evasion. This review discusses the role of circular RNAs (circRNAs) their involvement in circRNA/miRNA/mRNA axis during progression. As competitive endogenous (ceRNAs), circRNAs regulate gene expression cellular processes, proliferation, metastasis, apoptosis, resistance. Furthermore, we explore impact on tumor metabolic reprogramming influence microenvironment. We also summarize clinical prospects, challenges, future directions this field. A comprehensive understanding these complex interactions may provide new insights into diagnosis treatment RCC, ultimately overcoming existing challenges improving patient outcomes.
Язык: Английский
Процитировано
0
Molecular & Cellular Proteomics, Год журнала: 2025, Номер unknown, С. 100951 - 100951
Опубликована: Март 1, 2025
The human leukocyte antigen (HLA) processing and presentation machinery (APPM) is altered in various diseases response to drug treatments. Defects the may change levels or alter repertoire of presented peptides, globally an HLA allele restricted manner, with direct implications for adaptive immunity. In this study, we investigated immunopeptidome landscape across a panel isogenic HAP1 cell line clones each knock-out single gene encoding key protein APPM, including B2M, TAP1, TAP2, TAPBP, IRF2, PDIA3, ERAP1, GANAB, SPPL3, CANX, CALR. We applied immunopeptidomic proteomic assess successful knock-outs on level, understand how these proteins participate presentation, contextualize expression presentation. validated absence knocked-out respective samples found that knocking-out APPM component leads loss peptide subsets are normally control wild type cells. assessed immunopeptidomes qualitatively quantitatively, considering factors like diversity, length distribution, binding affinity endogenously expressed alleles demonstrated prominent allele-specific alterations several conditions. CALR, TAP1 led significant changes levels. Overall, work represents first systematic analysis individual components, knocked out under controlled conditions, affects peptidome. This approach could facilitate creation predictive tools capable prioritizing HLA-bound peptides likely be when defects occur, such as cancer viral infections.
Язык: Английский
Процитировано
0
Cancer Cell, Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
0