CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Aug. 19, 2022

Abstract Background Gastric cancer (GC) is one of the most common malignant tumors in China. Circular RNAs (circRNAs) are novel non-coding with important regulatory roles progression. IGF2BP3 has been found to play oncogenic various cancers including GC, while exact mechanism largely unknown. Methods The expression GC was evaluated by Western Blot and bioinformatics analysis. CircRNA profiles were screened via RIP-seq GC. Sanger sequencing, RNase R digestion, nucleo-plasmic separation RNA-FISH assays used detect existence circARID1A. RNA ISH assay employed test circARID1A paraffin-embedded tissues. Moreover, function on cellular proliferation assessed CCK-8, plate colony formation, EdU xenograft mouse model vivo. Furthermore, location or binding circARID1A, protein SLC7A5 RNA-FISH/IF pull-down assays. Results We identified a circRNA, that can bind protein. CircARID1A significantly upregulated tissues compared noncancerous positively correlated tumor length, volume, TNM stage. knockdown inhibited cells vitro vivo played an role IGF2BP3. Mechanistically, served as scaffold facilitate interaction between mRNA, finally increasing mRNA stability. Additionally, able directly through complementary base-pairing then formed circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex promoted regulating AKT/mTOR pathway. Conclusions Altogether, our data suggest involved proliferation, axis potential serve therapeutic target for

Language: Английский

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Targeting the “tumor microenvironment”: RNA-binding proteins in the spotlight in colorectal cancer therapy

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 131, P. 111876 - 111876

Published: March 16, 2024

Language: Английский

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Cooperation and competition by RNA-binding proteins in cancer

Seminars in Cancer Biology, Journal Year: 2022, Volume and Issue: 86, P. 286 - 297

Published: March 4, 2022

Language: Английский

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Proteome-Wide Identification of RNA-dependent proteins and an emerging role for RNAs in Plasmodium falciparum protein complexes

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 14, 2024

Abstract Ribonucleoprotein complexes are composed of RNA, RNA-dependent proteins (RDPs) and RNA-binding (RBPs), play fundamental roles in RNA regulation. However, the human malaria parasite, Plasmodium falciparum , identification characterization these particularly limited. In this study, we use an unbiased proteome-wide approach, called R-DeeP, a method based on sucrose density gradient ultracentrifugation, to identify RDPs. Quantitative analysis by mass spectrometry identifies 898 RDPs, including 545 not yet associated with RNA. Results further validated using combination computational molecular approaches. Overall, provides first snapshot protein-protein interaction network presence absence R-DeeP also helps reconstruct multiprotein co-segregation deciphers their RNA-dependence. One RDP candidate, PF3D7_0823200, is functionally characterized as true RBP. Using enhanced crosslinking immunoprecipitation followed high-throughput sequencing (eCLIP-seq), demonstrate that protein interacts various non-coding transcripts, var genes ap2 transcription factors.

Language: Английский

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iPSC-derived healthy human astrocytes selectively load miRNAs targeting neuronal genes into extracellular vesicles

Molecular and Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 129, P. 103933 - 103933

Published: April 23, 2024

Astrocytes are in constant communication with neurons during the establishment and maturation of functional networks developing brain. release extracellular vesicles (EVs) containing microRNA (miRNA) cargo that regulates transcript stability recipient cells. Astrocyte released factors thought to be involved neurodevelopmental disorders. Healthy astrocytes partially rescue Rett Syndrome (RTT) neuron function. EVs isolated from stem cell progeny also correct aspects RTT. cross blood-brain barrier (BBB) their is found peripheral blood which may allow non-invasive detection EV as biomarkers produced by healthy astrocytes. Here we characterize miRNA sequence motifs human astrocyte derived (ADEVs). First, induced Pluripotent Stem Cells (iPSC) were differentiated into Neural Progenitor (NPCs) subsequently using a rapid differentiation protocol. iPSC expressed specific markers, displayed intracellular calcium transients secreted ADEVs. miRNAs identified RNA-Seq on ADEVs target gene pathway analysis detected brain immune related terms. The profile was consistent identity, included approximately 80 relatively depleted suggestive passive loading. About 120 enriched motif discovered binding sites for RNA proteins FUS, SRSF7 CELF5. miR-483-5p most significantly This MECP2 expression has been differentially samples RTT patients. Our results identify potential selectively sorted implicate protein dependent mechanisms

Language: Английский

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Circ_0007432 promotes non-small cell lung cancer progression and macrophage M2 polarization through SRSF1/KLF12 axis

iScience, Journal Year: 2024, Volume and Issue: 27(6), P. 109861 - 109861

Published: April 30, 2024

Circular RNAs (circRNAs) plays critical roles in non-small cell lung cancer (NSCLC) development. Herein, we illustrated the effects of circ_0007432 on malignant features NSCLC. We found that played a promoting role NSCLC progression, lying accelerating viability, migration and invasion cells, M2 macrophage polarization, suppressing apoptosis enhancing tumor growth

Language: Английский

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Single-nucleus multiomic atlas of frontal cortex in amyotrophic lateral sclerosis with a deep learning-based decoding of alternative polyadenylation mechanisms

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 23, 2023

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two age-related fatal neurodegenerative disorders that lie on a shared disease spectrum. While both involve complex interactions between neuronal glial cells, the specific cell-type alterations their contributions to pathophysiology remain incompletely understood. Here, we applied single-nucleus RNA sequencing of orbitofrontal cortex, region affected in ALS-FTLD, map transcriptional signatures C9orf72-related ALS (with without FTLD) sporadic cases. Our findings reveal disease- cell-type-specific changes, with neurons exhibiting most pronounced alterations, primarily affecting mitochondrial function, protein homeostasis, chromatin remodeling. A comparison independent datasets from different cortical regions C9orf72 cases showed concordance several pathways, STMN2 NEFL showing consistent up-regulation brain subtypes. We also interrogated alternative polyadenylation (APA) as an additional layer regulation, demonstrating APA events not correlated identified gene expression changes. To interpret these events, developed APA-Net, deep learning model integrates transcript sequences RNA-binding profiles, revealing cell type-specific patterns regulation. atlas illuminates pathomechanisms ALS/FTLD, providing valuable resource for further investigation.

Language: Английский

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LARP4A and LARP4B in cancer: The new kids on the block

The International Journal of Biochemistry & Cell Biology, Journal Year: 2023, Volume and Issue: 161, P. 106441 - 106441

Published: June 24, 2023

Recent developments have mounted a stunning body of evidence underlying the importance RNA binding proteins (RBPs) in cancer research. In this minireview we focus on LARP4A and LARP4B, two paralogs belonging to superfamily La-related proteins, provide critical overview current research, including their roles pathogenesis cell proliferation, migration, cycle apoptosis. We highlight controversies surrounding LARP4B conclude that complex tumorigenesis are cell-, tissue- context-dependent, warning caution must be exercised before categorising either protein as an oncoprotein or tumour-suppressor. also reveal often been confused with one another, adding uncertainty delineating functions. suggest further functional mechanistic studies LARP4 present significant challenges for future investigations recognise vital contributions these RBPs

Language: Английский

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Inferring Potential Cancer Driving Synonymous Variants

Genes, Journal Year: 2022, Volume and Issue: 13(5), P. 778 - 778

Published: April 27, 2022

Synonymous single nucleotide variants (sSNVs) are often considered functionally silent, but a few cases of cancer-causing sSNVs have been reported. From available databases, we collected four categories sSNVs: germline, somatic in normal tissues, cancerous and putative cancer drivers. We found that screening for recurrence among patients, conservation the affected genomic position, synVep prediction (synVep is machine learning-based sSNV effect predictor) recovers driver (termed proposed drivers) previously unknown genes. Of 2.9 million COSMIC database, identified 2111 sSNVs. these, 326 could be further tagged possible RNA splicing effects, structural changes, RBP motifs. This list provides computational guidance prioritizing experimental evaluation synonymous mutations cancers. Furthermore, our novel potential genes, galvanized by mutations, may highlight yet unexplored mechanisms.

Language: Английский

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Role of CELF2 in ferroptosis: Potential targets for cancer therapy (Review)

International Journal of Molecular Medicine, Journal Year: 2023, Volume and Issue: 52(4)

Published: Aug. 9, 2023

Ferroptosis is a novel form of regulated cellular necrosis that plays critical role in promoting cancer progression and developing drug resistance. The main characteristic ferroptosis iron‑dependent lipid peroxidation caused by excess intracellular levels reactive oxygen species. CUGBP ELAV‑like family number 2 (CELF2) an RNA‑binding protein downregulated various types associated with poor patient prognoses. CELF2 can directly bind mRNA to variety control factors; however, direct evidence the regulatory currently limited. aim present review was summarise findings previous studies on its regulating redox homeostasis. may provide insight into possible mechanisms through which affects recommendations for future studies.

Language: Английский

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