Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)
Published: Dec. 20, 2024
Language: Английский
Cancer Communications, Journal Year: 2024, Volume and Issue: 44(9), P. 1018 - 1041
Published: July 19, 2024
Abstract Background N4‐acetylcytidine (ac4C) represents a novel messenger RNA (mRNA) modification, and its associated acetyltransferase N‐acetyltransferase 10 (NAT10) plays crucial role in the initiation progression of tumors by regulating mRNA functionality. However, hepatocellular carcinoma (HCC) development prognosis is largely unknown. This study aimed to elucidate NAT10‐mediated ac4C HCC provide promising therapeutic approach. Methods The levels were evaluated dot blot ultra‐performance liquid chromatography‐tandem mass spectrometry with harvested tissues. expression NAT10 was investigated using quantitative real‐time polymerase chain reaction, western blotting, immunohistochemical staining across 91 cohorts patients. To explore underlying mechanisms NAT10‐ac4C HCC, we employed comprehensive approach integrating acetylated immunoprecipitation sequencing, sequencing ribosome profiling analyses, along immunoprecipitation, pull‐down, spectrometry, site‐specific mutation analyses. drug affinity responsive targets stability, cellular thermal shift assay, surface plasmon resonance assays performed assess specific binding Panobinostat. Furthermore, efficacy targeting for treatment elucidated through vitro experiments cells vivo mouse models. Results Our investigation revealed significant increase both level HCC. Notably, elevated poor outcomes Functionally, silencing suppressed proliferation metastasis vivo. Mechanistically, stimulates modification within coding sequence (CDS) high mobility group protein B2 (HMGB2), which subsequently enhances HMGB2 translation facilitating eukaryotic elongation factor 2 (eEF2) sites on mRNA's CDS. Additionally, high‐throughput compound library screening Panobinostat as potent inhibitor modification. inhibition significantly attenuated growth Conclusions identified oncogenic epi‐transcriptome axis involving NAT10‐ac4C/eEF2‐HMGB2, pivotal metastasis. validates potential this treatment.
Language: Английский
Citations
8
MedComm – Oncology, Journal Year: 2025, Volume and Issue: 4(1)
Published: Feb. 17, 2025
ABSTRACT Metastasis remains a leading cause of cancer‐related deaths, defined by complex, multi‐step process in which tumor cells spread and form secondary growths distant tissues. Despite substantial progress understanding metastasis, the molecular mechanisms driving this development effective therapies remain incompletely understood. Elucidating pathways governing metastasis is essential for discovery innovative therapeutic targets. The rapid advancements sequencing technologies expansion biological databases have significantly deepened our drivers associated drug resistance. This review focuses on particularly roles genetic mutations, epigenetic changes, post‐translational modifications progression. We also examine how microenvironment influences metastatic behavior explore emerging strategies, including targeted immunotherapies. Finally, we discuss future research directions, stressing importance novel treatment approaches personalized strategies to overcome improve patient outcomes. By integrating contemporary insights into basis innovation, provides comprehensive framework guide clinical cancer.
Language: Английский
Citations
0
Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(6)
Published: March 20, 2025
Abstract RNA modifications play crucial roles in metabolism, structure, and functions. N4-acetylcytidine (ac4C) have been shown to enhance stability translation efficiency of messenger RNAs viral RNAs. However, the relationship between ac4C alternative processing remains unexplored. Here, N-acetyltransferase 10 (NAT10) its catalyzed on minute virus canines (MVC) were regulate DNA replication processing, including both splicing polyadenylation. Through acRIP-seq RedaC:T-seq, functional ac4C-modified residue 3311 was identified characterized, which affected MVC rather than altered stability. Ac4C modification at nt revealed participate NP1-mediated without influencing affinity NP1. Meanwhile, CPSF5 interact with NP1 mediate an ac4C-dependent manner. Further vitro assays showed that recruited RNAs, promoted specific binding target region, ensured precise processing. This study not only reveals functions NAT10 but also elucidates mechanisms by orchestrate proteins host factors for efficient
Language: Английский
Citations
0
Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)
Published: March 6, 2025
Emerging evidence has confirmed the inextricable connection between N4-acetylcytidine (ac4C) mRNA modification and clinical characteristics of malignancies. Nonetheless, it is uncertain whether how ac4C patterns affect outcomes in melanoma patients. This research integrated single-cell sequencing data transcriptomics to pinpoint ac4C-related genes (acRG) linked progression evaluate their implications. Cells with elevated acRG score were predominantly located within melanocytes cluster. Intercellular communications other cell subtypes markedly strengthened acRG-high group. We developed an excellent acRG-related signature (acRGS) utilizing a comprehensive set 101 algorithm combinations derived from 10 machine learning algorithms. Hereby, acRGS, including MYO10, ZNF667, MRAS, SCO2, MAPK10, PNMA6A, KPNA2, NT5DC2, BAIAP2L2 NDST3, delineated ac4C-associated melanoma. The acRGS possesses distinctly superior performance 120 previously reported signatures could predict overall survival patients across four external datasets. substantial associations among immune checkpoint genes, infiltration, tumor mutation burden indicate that helpful identifying who are sensitive immunotherapy. Besides, we MYO10 was mainly overexpressed tissues, positively correlated malignant phenotypes unfavorable prognosis Silencing expression inhibited proliferation, migration invasion vitro as well growth vivo. Taken together, function reliable prospective tool improve for individuals.
Language: Английский
Citations
0
Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)
Published: March 31, 2025
High mobility group box 2 (HMGB2), one of the HMGB domain proteins, may play a significant role in cancer development and progression. Recent scientific investigations have hinted at potential clinical relevance HMGB2, particularly patients where its expression levels been observed to be elevated. However, precise impact HMGB2 on prognosis tumors remains an area ongoing research. To best our understanding, study represents meta-analysis that elucidates connection between outcomes diverse types. We executed thorough systematic search literature across PubMed, Web Science, Embase, CNKI, Wanfang databases. Following this, we conducted quantitative using statistical tools such as StataMP16 RevMan5.3. The primary focus analysis was assess relationship overall survival (OS), disease-free (DFS), well various clinicopathological characteristics by calculating hazard ratio (HR). Additionally, validated findings examining patterns different types Gene Expression Profiling Interactive Analysis (GEPIA) online platform. Our incorporated data from 17 studies, encompassing total 2555 patients. results revealed statistically association high shorter OS (HR, 1.40 ;95% CI: 1.10-1.70; P < 0.001), especially digestive ( HR, 2.09 (95% 1.54-2.63; I2 = 0.0%,P 0.424). Furthermore, GEPIA demonstrated consistent upregulation most types, with downregulation LAML. underscore detrimental correlation cancers. This discovery could pave way for innovative prognostic biomarkers therapeutic targets specifically target offering new avenues management treatment
Language: Английский
Citations
0
Oncogene, Journal Year: 2024, Volume and Issue: 43(48), P. 3498 - 3516
Published: Oct. 10, 2024
Language: Английский
Citations
3
Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)
Published: Nov. 11, 2024
Metabolic dysfunction associated steatotic liver disease (MASLD), closely linked to excessive lipogenesis, induces chronic disease. MASLD often cause other metabolic diseases, such as cardiovascular disease, diabetes and obesity. However, the mechanism of N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) mRNA modification in lipogenesis has not been fully elucidated. This study investigated role NAT10 targeting ac4C modification. The expression mouse was assessed after a 12-week high-fat diet. In addition, also detected AML12 hepatocytes cells were treated with 150 µmol/L palmitic acid (PA). performed by dot blotting. Oil red O staining Srebf1, Acaca Fasn used assess overexpression or knockdown. acRIP-PCR RIP-PCR verify Srebf1 Scap NAT10. Furthermore, evaluated AAV-mediated target knockdown treating specific inhibitor, Remodelin. revealed that is significantly upregulated drastically increased PA. Silencing notably inhibited liver. NAT10-RIP-PCR modified mRNA, critical modulator regulate lipogenesis. Besides, Remodelin strongly including TG, serum ALT, AST, TG TC level glucose metabolism. mediates thereby affecting provided new for treatment MASLD.
Language: Английский
Citations
2
Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)
Published: Dec. 20, 2024
Language: Английский
Citations
0