RNA-binding protein CCDC137 activates AKT signaling and promotes hepatocellular carcinoma through a novel non-canonical role of DGCR8 in mRNA localization

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: Aug. 5, 2023

Abstract Background RNA binding proteins (RBPs)—regulated gene expression play a vital role in various pathological processes, including the progression of cancer. However, RBP hepatocellular carcinoma (HCC) remains much unknown. In this study, we aimed to explore contribution CCDC137 HCC development. Methods We analyzed altered level and clinical significance database specimens. vitro cell assays vivo spontaneous mouse models were used assess function CCDC137. Finally, molecular mechanisms how regulates promotes was explored. Results is aberrantly upregulated correlates with poor outcomes patients. markedly promoted proliferation vivo. Mechanistically, binds FOXM1 , JTV1 LASP1 FLOT2 mRNAs, which revealed by APOBEC1-mediated profiling, increase their cytoplasmic localization thus enhance protein expressions. Upregulation FOXM1, JTV1, subsequently synergistically activate AKT signaling promote HCC. Interestingly, found that microprocessor DGCR8 has novel non-canonical mRNA subcellular localization, mediates distribution mRNAs regulated Conclusions Our results identify critical proliferation-related reveal CCDC137/DGCR8/mRNA localization/AKT axis progression, provide potential target for therapy.

Language: Английский

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ZCCHC4 regulates esophageal cancer progression and cisplatin resistance through ROS/c-myc axis

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 12, 2025

Abstract Zinc finger CCHC-type containing 4 (ZCCHC4) is a newly discovered N 6 -methyladenosine (m A) RNA methyltransferase (MTase), which possesses an m A MTase domain and RNA-binding protein (RBP) Znf domain. Aberrantly expressed ZCCHC4 has been found to be correlated with poor prognosis chemoresistance in various tumors, such as hepatocellular carcinoma, lung cancer colorectal cancer. However, the expression functional analysis of role esophageal (ESCA) still elusive. The tissues was evaluated by qPT-PCR western blot. Serum tumor markers are detected electrochemiluminescence immunoassay. Relationship between pathway enrichment were analyzed R. reactive oxygen species (ROS), cell proliferation, cycle apoptosis squamous carcinoma (ESCC) cells tested CCK8 assay flow cytometry assay. Aberrant associated stages, lymph node metastasis (LNM), histology, poorer Overall Survival (OS) mRNA level patients correlates serum carcinoembryonic antigen (CEA) levels, Squamous Cell Carcinoma (SCC) markers, tissue polypeptide (TPA) levels. Knockdown induces DNA damage, leading elevation turn triggers S-phase arrest, enhances apoptosis, augments sensitivity cisplatin treatment, inhibits proliferation cells. Conversely, overexpression promotes increases resistance Furthermore, scavenging ROS reverses effects downregulation on both Additionally, progression reduces vivo. In summary, leads increased ESCC cisplatin, cells, potentially via ROS/c-myc axis. study suggests potential adjunctive for diagnosis treatment aids further understanding underlying mechanisms ESCA progression.

Language: Английский

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Tetrahedral DNA nanostructure based siRNA delivery vehicle for braf gene silencing and MEK-ERK pathway inhibition in the treatment of refractory thyroid cancer

Nano Today, Journal Year: 2025, Volume and Issue: 62, P. 102694 - 102694

Published: Feb. 28, 2025

Language: Английский

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Histone Phosphorylation in DNA Damage Response

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2405 - 2405

Published: March 7, 2025

The DNA damage response (DDR) is crucial for maintaining genomic stability and preventing the accumulation of mutations that can lead to various diseases, including cancer. DDR a complex cellular regulatory network involves sensing, signal transduction, repair, cell cycle arrest. Modifications in histone phosphorylation play important roles these processes, facilitating repair factor recruitment, chromatin remodeling, regulation. precise regulation critical effective damage, integrity maintenance, prevention diseases such as cancer, where mechanisms are often compromised. Thus, understanding provides insights into offers potential therapeutic targets associated with instability, cancers.

Language: Английский

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A Metformin-Based Multifunctional Nanoplatform as a DNA Damage Amplifier for Maximized Radio-Immunotherapy to Overcome Radiotherapy Resistance

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Radiotherapy (RT) has been highlighted to be an effective strategy for antitumor immunity activation by causing direct DNA damages, but it generally suffers from low response rates due the compromised cytosolic (cDNA) recognition cyclic GMP-AMP synthase (cGAS). Simultaneous repair and clearance system regulation enhanced cDNA accumulation is a useful approach improve immune rates, which remains seldom reported our knowledge. Here, we report construction of metformin (MET)-based multifunctional nanocomplex, CS-MET/siTREX1 (CSMT), consisting biguanide-decorated CS (CS-MET) as vector 3'-5' exonuclease TREX1 siRNA (siTREX1) therapeutic gene RT-induced enhancement amplifying initial damage signals. The uniqueness this study development CSMT specific amplifier promote maximizing radio-immunotherapy circumventing RT resistance. Specifically, nanocomplexes show not only transfection efficiency MET modification also synergistic effects including MET's inhibition on siTREX1's attenuation clearance, leads greatest inhibitory effect in Hepa1-6 proximal/distal tumor model with high growth (TGI) value 99.1% primary significantly distal inducing immunogenic cell death (ICD), promoting tumor-associated neutrophil (TAN) polarization, stimulating tumor-specific memory T-cell generation. Overall, developed herein hold great translatable promises overcoming resistance clinics.

Language: Английский

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RNA-binding proteins and autophagy in lung cancer: mechanistic insights and therapeutic perspectives

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 24, 2025

Lung cancer remains a leading cause of cancer-related mortality worldwide. Its progression is intricately associated with the dynamic regulation autophagy and RNA-binding proteins (RBPs), which play crucial roles in mRNA stability, alternative splicing, cellular stress responses. This review aims to systematically analyze mechanisms through RBPs contribute lung explore potential therapeutic strategies targeting these pathways. We reviewed recent studies on molecular by regulate tumor proliferation, metabolic adaptation, their interaction autophagy. The also examines dual cancer, highlighting its context-dependent effects cell survival death. interactions regulatory networks between involve multiple levels regulation. can directly influence processes act as microRNA (miRNA) sponges stability. modulation affects expression autophagy-related genes (ATGs) autophagosome formation. Additionally, participate complex non-coding RNAs (ncRNAs), including long (lncRNAs), circular (circRNAs), other proteins. proposes innovative that combine RBP-targeting approaches (e.g., small molecule inhibitors, CRISPR gene editing) modulators mTOR chloroquine) enhance treatment efficacy. Nanoparticle drug delivery systems epigenetic offer further opportunities for targeted interventions. lays theoretical foundation advancing research provides novel insights into synergistic therapies target both improve outcomes cancer.

Language: Английский

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Exploring RNA binding proteins in hepatocellular carcinoma: insights into mechanisms and therapeutic potential

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: April 24, 2025

Abstract Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is linked to elevated global incidence and mortality rates. Elucidating intricate molecular pathways that drive progression HCC imperative for devising targeted effective therapeutic interventions. RNA-binding proteins (RBPs) serve as pivotal regulators post-transcriptional processes, influencing various cellular functions. This review endeavors provide a comprehensive analysis expression, function, potential implications RBPs in HCC. We discuss classification diverse roles RBPs, with particular focus on key implicated their association disease progression. Additionally, we explore mechanisms by which contribute HCC, including impact gene cell proliferation, metastasis, angiogenesis, signaling pathways, modifications. Importantly, examine targets prognostic biomarkers, offering insights into relevance treatment. Finally, outline future research directions, emphasizing need further investigation functional clinical translation personalized therapy. highlights role novel avenues improve patient outcomes. Graphical

Language: Английский

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Roles of RNA-binding proteins in neurological disorders, COVID-19, and cancer

Human Cell, Journal Year: 2022, Volume and Issue: 36(2), P. 493 - 514

Published: Dec. 18, 2022

Language: Английский

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PM2.5-derived exosomal long noncoding RNA PAET participates in childhood asthma by enhancing DNA damage via m6A-dependent OXPHOS regulation

Environment International, Journal Year: 2023, Volume and Issue: 183, P. 108386 - 108386

Published: Dec. 12, 2023

Fine particulate matter (PM2.5) is known to enhance DNA damage levels and involved in respiratory diseases. Exosomes can carry noncoding RNAs, especially long RNAs (lncRNAs), as regulators of damage, which participate However, their role PM2.5-induced childhood asthma remains unclear. We performed RNA-seq profile aberrantly expressed exosomal lncRNAs derived from PM2.5-treated human bronchial epithelial (HBE) cell models. The was determined a case–control study. intercellular communication mechanisms lncRNA on were vitro. secreted by HBE cells (PM2.5-Exos) could increase the recipient promote expression airway remodeling-related markers sensitive smooth muscle (HBSMCs). LncRNA PM2.5-associated transcript (PAET) highly PM2.5-Exos associated with PM2.5 exposure asthma. Mechanistically, PAET promoted methyltransferase-like 3 (METTL3) accumulation increasing its stability, stimulated N6-methyladenosine (m6A) modification cytochrome c oxidase subunit 4I1 (COX4I1), COX4I1 decreased mechanism dependent m6A "reader" YTH domain family (YTHDF3). deficiency subsequently disrupted oxidative phosphorylation (OXPHOS), resulting attenuated adenosine triphosphate (ATP) production reactive oxygen species (ROS), increased levels. This comprehensive study extends understanding via identifies potential target for

Language: Английский

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Dimeric oxyberberine CT4-1 targets LINC02331 to induce cytotoxicity and inhibit chemoresistance via suppressing Wnt/β-catenin signaling in hepatocellular carcinoma

Archives of Toxicology, Journal Year: 2023, Volume and Issue: 97(6), P. 1627 - 1647

Published: April 30, 2023

Language: Английский

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