GC-derived exosomal circMAN1A2 promotes cancer progression and suppresses T-cell antitumour immunity by inhibiting FBXW11-mediated SFPQ degradation

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Янв. 25, 2025

Abstract Background Exosomes, as extracellular membrane vesicles, play important roles in intercellular communication and can influence tumour progression. Circular RNAs (circRNAs) have been reported various malignancies are also components of exosomes. However, the role exosomal circRNAs gastric cancer (GC) progression has not completely clarified. Methods The enriched GC were identified using circRNA sequencing. biological function circMAN1A2 was investigated a series vitro vivo experiments. PKH-67 staining used to label molecular mechanism via mass spectrometry, immunoprecipitation, Western blot, single-cell RNA-sequencing data analyses. Results In our study, we determined that (hsa_circ_0000118) GC-derived Higher expression related poor survival patients (HR = 2.917, p 0.0120). Exosomal promoted suppressed antitumour activity T cells. Moreover, bound SFPQ cells cells, promoting G1/S phase transition cell cycle while inhibiting activation receptor signalling pathway decrease activity. Mechanistically, competed with FBXW11 for binding SFPQ, preventing FBXW11-mediated k48-linked ubiquitination protein degradation, thereby stabilizing expression. Conclusions Our work confirms critical immunosuppression GC. This novel axis circMAN1A2-SFPQ provides new insights into circRNA-based diagnostic therapeutic strategies.

Язык: Английский

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Noncoding RNA (ncRNA)-mediated regulation of TLRs: critical regulator of inflammation in tumor microenvironment

Medical Oncology, Год журнала: 2025, Номер 42(5)

Опубликована: Март 31, 2025

Язык: Английский

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Noncoding RNAs in sepsis-associated acute liver injury: Roles, mechanisms, and therapeutic applications

Pharmacological Research, Год журнала: 2025, Номер 212, С. 107596 - 107596

Опубликована: Янв. 10, 2025

Sepsis is a life-threatening syndrome characterized by organ dysfunction caused dysregulated host response to infection. Sepsis-associated acute liver injury (SA-ALI) frequent and serious complication of sepsis that considerably impacts both short-term long-term survival outcomes. In intensive care units (ICUs), the mortality rate patients with SA-ALI remains high, mostly due absence effective early diagnostic markers suitable therapeutic strategies. Recent studies have demonstrated importance non-coding RNAs (ncRNAs) in development progression SA-ALI. This review focuses on critical roles ncRNAs, including microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), regulating "cytokine storms", oxidative stress, mitochondrial dysfunction, programmed cell death SA-ALI, summarizes current state limitations existing lncRNAs circRNAs By integrating advancements high-throughput sequencing technologies, this provides novel insights into dual potential ncRNAs as biomarkers targets, offers new ideas for diagnosis treatment research highlights challenges clinical translation.

Язык: Английский

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Past, present, and future strategies for detecting and quantifying circular RNA variants

FEBS Journal, Год журнала: 2025, Номер unknown

Опубликована: Фев. 11, 2025

Circular RNAs (circRNAs) are a family of covalently closed RNA transcripts ubiquitous across the eukaryotic kingdom. CircRNAs generated by class alternative splicing called backsplicing, with resultant circularization part parental producing characteristic backsplice junction (BSJ). Because noncontiguous sequence BSJ respect to DNA genome, circRNAs remained hidden in plain sight through over decade next-generation sequencing, yet 3 million unique circRNA have been illuminated past alone. expressed cell type-specific manner, highly stable, many examples being evolutionarily conserved and/or functional specific contexts. However, can be very lowly and predictions context from BSJ-spanning reads alone confound extrapolation exact composition transcript. For these reasons, ultrasensitive detection, combined enrichment, bespoke bioinformatics pipelines and, more recently, long-read, processive sequencing is becoming critical for complete characterization all variants. Concomitantly, need targeted detection quantification has sparked numerous laboratory-based commercial approaches visualize cells quantify them biological samples, including biospecimens. This review focuses on advancements circRNAs, particular focus recent bolster variants accurately normalize between libraries.

Язык: Английский

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Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities

MedComm, Год журнала: 2024, Номер 5(12)

Опубликована: Ноя. 24, 2024

Exosomes can regulate the malignant progression of tumors by carrying a variety genetic information and transmitting it to target cells. Recent studies indicate that exosomal circular RNAs (circRNAs) multiple biological processes in carcinogenesis, such as tumor growth, metastasis, epithelial-mesenchymal transition, drug resistance, autophagy, metabolism, angiogenesis, immune escape. In microenvironment (TME), circRNAs be transferred among cells, endothelial cancer-associated fibroblasts, microbiota, affecting initiation progression. Due high stability widespread presence circRNAs, they hold promise biomarkers for diagnosis prognosis prediction blood urine. addition, designing nanoparticles targeting utilizing derived from cells or stem provide new strategies cancer therapy. this review, we examined crucial role regulating tumor-related signaling pathways summarized transmission between various types their impact on TME. Finally, our review highlights potential diagnostic prognostic biomarkers, well suggesting clinical

Язык: Английский

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hsa_circ_0008305 facilitates the malignant progression of hepatocellular carcinoma by regulating AKR1C3 expression and sponging miR-379-5p

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 8, 2025

Circular RNAs (circRNAs) are widely involved in diverse biological processes of cancers. Nonetheless, the potential function hsa_circ_0008305 hepatocellular carcinoma (HCC) remains largely unknown. This study aims to elucidate role and underlying mechanism HCC. Our findings reveal that novel circRNA (circPTK2) is significantly upregulated HCC tissues, with its elevated expression being positively correlated advanced tumor T stage vascular invasion. The circular characteristics subcellular localization was determined by RNase R treatment RNA nucleocytoplasmic separation. Further functional assays, including CCK8, EdU, colony formation scratch-healing, transwell Xenograft models were conducted explore functions circPTK2. regulatory mechanisms circPTK2 elucidated through sequencing, enrichment analysis, dual luciferase reporter assay. indicate stably localized cytoplasm. Functionally, circPKT2 promoted cells proliferation, migration, invasion both vitro vivo. Mechanistically, found regulates AKR1C3 acting as a sponge for miR-379-5p. Inhibition miR-379-5p mitigates effects induced identified direct target miR-379-5p, silencing overturns promotion progression inhibitor. In conclusion, our results revealed facilitates malignant via sponging up-regulate expression.

Язык: Английский

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Liquid biopsy: an emerging field with new opportunities for cancer diagnosis and prognosis

Asia-Pacific Journal of Oncology, Год журнала: 2025, Номер unknown, С. 9 - 17

Опубликована: Янв. 14, 2025

Cancer grades among the deadliest diseases, globally causing death of a over million people each year. Early diagnosis has been considered ideal for efficient treatment as during later stages chances become limited. However, gold standard tissue biopsy various limitation instance, late-stage and its intrusive operation making it unfit repeated sampling. Scientists are passionately looking new technologies techniques cancer prognosis. Liquid emerged diagnostic prognostic tool cancer, that relies on body fluids to identify biomarkers cancer. It offers advantages like non-invasive operation, timely detection, amenable sampling, covers tumor heterogeneity. Wide attention garnered by liquid is undergoing rapid progress in list target biomarkers. The most common circulating cells, DNA, exosomes, educated platelets, non-coding RNAs (miRNA, lncRNA etc.). Each these have unique advantages, indeed technology future with clinical utility. In this article, we tried provide thorough introduction markers, highlighted deployed biopsy, briefly overview their implications indispensable entities diverse types Moreover, discussed prospects revolutionary realm treatment.

Язык: Английский

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Profiling and bioinformatics analyses of circular RNAs in myocardial ischemia/reperfusion injury model in mice

World Journal of Cardiology, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 21, 2025

BACKGROUND Myocardial ischemia/reperfusion (I/R) injury, which is associated with high morbidity and mortality, a main cause of unexpected myocardial injury after acute infarction. However, the underlying mechanism remains unclear. Circular RNAs (circRNAs), are formed from protein-coding genes, can sequester microRNAs or proteins, modulate transcription interfere splicing. Authoritative studies suggest that circRNAs may play an important role in I/R injury. AIM To explore METHODS We constructed model using ligation left anterior descending coronary artery, evaluated success validated triphenyltetrazolium chloride hematoxylin-eosin staining. Then, ventricular samples different groups were selected for mRNA-sequence, differential gene screening was performed on obtained results. The differentially mRNAs divided into up-regulated down-regulated according to their expression levels, Gene Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) functional enrichment analysis performed, respectively. circRNA microRNA (miRNA) paired analysis, binding sites miRNA mRNA virtual screened. Finally, circRNA, by ceRNA mutual most useful network. RESULTS used RNA sequencing array investigate signatures three group sham group. A total 142 upregulated 121 downregulated found be expressed (fold change ≥ 2, P < 0.05). GO KEGG analyses these performed. revealed involved mainly cellular intracellular processes. demonstrated 6 top 20 pathways correlated cell apoptosis. Furthermore, circRNA-miRNA coexpression network based genes constructed, revealing mmu-circ-0001452, mmu-circ-0001637, mmu-circ-0000870 might key regulators CONCLUSION This research provides new insights I/R, expected therapeutic targets

Язык: Английский

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Circular RNAs in cancer

MedComm, Год журнала: 2025, Номер 6(2)

Опубликована: Фев. 1, 2025

Abstract Circular RNA (circRNA), a subtype of noncoding RNA, has emerged as significant focus in research due to its distinctive covalently closed loop structure. CircRNAs play pivotal roles diverse physiological and pathological processes, functioning through mechanisms such miRNAs or proteins sponging, regulation splicing gene expression, serving translation templates, particularly the context various cancers. The hallmarks cancer comprise functional capabilities acquired during carcinogenesis tumor progression, providing conceptual framework that elucidates nature malignant transformation. Although numerous studies have elucidated role circRNAs cancers, their functions development chemoradiotherapy resistance remain unexplored clinical applications circRNA‐based translational therapeutics are still infancy. This review provides comprehensive overview circRNAs, covering biogenesis, unique characteristics, functions, turnover mechanisms. We also summarize involvement relevance biomarkers therapeutic targets, especially thyroid (TC). Considering potential fascination therapeutics, “Ying‐Yang” dynamic regulations TC warrant vastly dedicated investigations.

Язык: Английский

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Circ_0070934 Regulates the Proliferation, Metastasis, and Epithelial–Mesenchymal Transition of Colorectal Cancer Cells by Targeting miR‐203a‐3p/HOXA13 Axis

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(2)

Опубликована: Фев. 1, 2025

ABSTRACT The present work explored the functions of circ_0070934 in regulating malignant phenotype colorectal cancer (CRC) cells and its underlying mechanisms. Gene expression data set was acquired based on Expression Omnibus (GEO) database for examining levels within CRC tissues through quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR). Kaplan–Meier curve log‐rank test were adopted assessing patient prognosis level. Functional assays including Cell Counting Kit (CCK)‐8, EdU incorporation, Transwell invasion, scratch conducted to determine cell malignancy. Molecular interactions predicted using circInteractome StarBase databases, validated luciferase reporter assay. Circ_0070934 upregulated tissues, which related a dismal prognostic outcome patients. Knocking down inhibited proliferation, epithelial–mesenchymal transition (EMT), migration. Further, we identified miR‐203a‐3p as target miRNA circ_0070934, negatively regulated Homeobox A13 (HOXA13) expression. miR‐203a‐3p/HOXA13 axis mediates function modulating These revealed that important maintaining cells, knockdown undermined Targeting circ_0070934/miR‐203a‐3p/HOXA13 is promising intervention approach managing CRC.

Язык: Английский

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