Biomolecules, Год журнала: 2024, Номер 14(10), С. 1319 - 1319
Опубликована: Окт. 17, 2024
N6-methyladenosine (m
Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)
Опубликована: Июнь 20, 2024
Abstract Background KIAA1429, a regulatory subunit of the N 6 -methyladenosine (m A) methyltransferase complex, has been implicated in progression various cancers. However, role KIAA1429 gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate GC elucidate mechanisms. Methods The expression patterns clinical relevance were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), bioinformatic analysis. In vitro vivo loss- gain-of-function assays, m A dot blot methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter stability (RIP) pull-down assays performed biological functions molecular GC. Results Both mRNA protein greater tissues than normal tissues. High correlated positively with poor prognosis patients. not only promoted cell proliferation, colony formation, G2/M cycle transition, migration, invasion but also enhanced tumor growth metastasis vivo. Mechanistically, increased level RASD1 an A-YTHDF2-dependent manner, thereby upregulating expression. knockdown partially rescued knockdown-induced impairment pro‑oncogenic ability cells. levels negatively Conclusions plays by downregulating through destabilizing manner. may serve as prognostic biomarker therapeutic target for
Язык: Английский
Процитировано
6
Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)
Опубликована: Июль 25, 2024
The escalating prevalence of metabolic diseases has led to a rapid increase in non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (NASH-HCC). While oxaliplatin (OXA)-based hepatic arterial infusion chemotherapy (HAIC) shown promise advanced-stage HCC patients, its efficacy NASH-HCC remains uncertain. This study aims assess the effectiveness OXA-based HAIC and elucidate mechanisms underlying OXA resistance NASH-HCC. key lncRNAs were screened through RNA-seq analysis NASH/non-NASH OXA-sensitive/OXA-resistant (OXA-S/R) tissues. biological functions lnc-OXAR (OXA resistance-related lncRNA NASH-HCC) verified series vitro vivo experiments. molecular mechanism was elucidated by fluorescence situ hybridization, immunoprecipitation-mass spectrometry (FISH), Immunoprecipitation-Mass Spectrometry (IP-MS), RNA pulldown, immunoprecipitation (RIP), methylated sequencing (MeRIP-Seq) dual-luciferase reporter assay. exhibited reduced responsiveness compared non-NASH HCC. We identified validated novel transcript namedlnc-OXAR, which played crucial role conferring Inhibition suppressed cell growth restored sensitivity both mouse models vitro. Mechanistically, recruited Ku70 cystatin A (CSTA), preventing degradation facilitating DNA double-strand break (DSB) repair, thereby promoting Additionally, WTAP-mediated m6A modification enhanced stability an IGF2BP2-dependent manner. Notably, silencing significantly response patient-derived xenograft (PDX) derived from treatment can be attributed upregulation lnc-OXAR. Our findings provide rationale for stratifying patients undergoing based on etiology. Lnc-OXAR holds as target overcoming improving prognosis.
Язык: Английский
Процитировано
6
Cell Biology and Toxicology, Год журнала: 2024, Номер 40(1)
Опубликована: Июль 26, 2024
Abstract Objective Multiple myeloma (MM) is a deadly plasma cell malignancy with elusive pathogenesis. N6-methyladenosine (m6A) critically engaged in hematological malignancies. The function of KIAA1429, the largest component methyltransferases, unknown. This study delved into mechanism KIAA1429 MM, hoping to offer novel targets for MM therapy. Methods Bone marrow samples were attained from 55 patients and 15 controls. YTHDF1, FOXM1 mRNA levels detected their correlation was analyzed. Cell viability, proliferation, cycle, apoptosis testified. Glycolysis-enhancing genes (HK2, ENO1, LDHA), lactate production, glucose uptake evaluated. interaction between m6A-modified level, stability assayed. A transplantation tumor model built confirm KIAA1429. Results at high cells linked poor prognoses. knockdown restrained arrested G0/G1 phase, increased apoptosis. positively glycolysis-enhancing genes. genes, uptake, production repressed after knockdown, along reduced stability. YTHDF1 recognized KIAA1429-methylated raised Knockdown curbed aerobic glycolysis malignant behaviors cells, which nullified by overexpression. also inhibited growth animal experiments. Conclusion reduces expression through YTHDF1-mediated m6A modification, thus inhibiting tumorigenesis. Graphical tumorigenesis
Язык: Английский
Процитировано
5
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(4), С. 4225 - 4225
Опубликована: Фев. 20, 2023
RNA methylations play critical roles in processes, including splicing, nuclear export, nonsense-mediated decay, and translation. Regulators of have been shown to be differentially expressed between tumor tissues/cancer cells adjacent tissues/normal cells. N6-methyladenosine (m6A) is the most prevalent internal modification RNAs eukaryotes. m6A regulators include writers, demethylases, binding proteins. Since important regulating expression oncogenes suppressor genes, targeting can a strategy for developing anticancer drugs. Anticancer drugs are clinical trials. regulator-targeting could enhance effects current chemotherapy This review summarizes cancer initiation progression, autophagy, drug resistance. The also discusses relationship autophagy resistance, effect high levels on potential values as diagnostic markers therapeutic targets.
Язык: Английский
Процитировано
11
DNA and Cell Biology, Год журнала: 2025, Номер 44(5), С. 229 - 237
Опубликована: Март 5, 2025
Wilms' tumor (WT) is the most prevalent renal cancer in children. Numerous studies have shown that vir-like n6-methyladenosine (m6A) methyltransferase-associated protein (VIRMA), a necessary component and largest methyltransferase, contributes to advancement of multiple cancers. However, its function has not been characterized WT. Hence, we examined potential role VIRMA WT by analyzing effect on m6A modification stearoyl-CoA desaturase (SCD). We utilized bioinformatics narrow 12 differentially expressed (DE) genes single gene. The expressions SCD were analyzed via quantitative real-time PCR western blotting. influence malignancy attributes cells adenosine 5'-monophosphate-activated kinase (AMPK) signaling was assessed through Cell counting Kit-8, Ethynyl-2'-deoxyuridine, transwell, blotting assays. specific interactions between confirmed methylated RNA immunoprecipitation, blotting, stability assays, followed rescue experiments show underlying mechanisms. expression found be elevated samples. Furthermore, silencing mitigated malignant characteristics while increasing levels key AMPK molecules. Moreover, also upregulated samples demonstrated positive association with expression. relative enrichment m6A, protein, mRNA enhanced VIRMA-overexpressed cells. Mechanically, overexpression accelerated phenotypes interacting SCD. Overall, results demonstrate VIRMA-mediated methylation promotes progression modulating pathway.
Язык: Английский
Процитировано
0
Hereditas, Год журнала: 2025, Номер 162(1)
Опубликована: Март 11, 2025
Abstract Background The screening and monitoring of gastric cancer is still a clinical challenge. Both N 6 -methyladenosine (m A) lncRNAs have been evidenced as critical regulators cancer, but their interaction potential in modulating tumor progression remain unclear. This study aimed to evaluate the function lncRNA LINC00968 biological processes, we discovered role KIAA1429, typical m A eraser, mediating function. Materials methods expression was assessed using PCR regulated by cell transfection. Cellular processes were evaluated CCK8 Transwell assays. modification with KIAA1429 identified Methylated RNA immunoprecipitation-qPCR. regulatory effect on miR-3202 VIRMA estimated luciferase reporter assay. Results Significantly increased observed cells. Silencing suppressed growth motility. A-modified sites predicted overexpressing enhanced enrichment stability reversed knockdown LINC00968. overexpression could attenuate inhibitory cellular processes. negatively regulate miR-3202, which further VIRMA, coding gene Conclusions contributes metastasis mediated KIAA1429-mediating miR-3202/VIRMA axis.
Язык: Английский
Процитировано
0
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(5), С. 167793 - 167793
Опубликована: Март 14, 2025
Язык: Английский
Процитировано
0
Frontiers in Pharmacology, Год журнала: 2025, Номер 16
Опубликована: Апрель 28, 2025
Gastrointestinal (GI) tumors represent a significant global health burden and are among the leading causes of cancer-related mortality worldwide. their drug resistance is one major challenges in cancer therapy. In recent years, epigenetic modifications, especially N6-methyladenosine (m6A) RNA have become hot research topic. m6A modification plays an important role gene expression progression by regulating splicing, translation, stability, degradation, which regulated "writers," "erasers" "readers." GI tumors, to chemotherapy, targeted therapy, immunotherapy closely associated with modification. Therefore, molecular mechanism its development provide new therapeutic strategies for overcoming efficacy tumors. this review, biological functions were explored, specific mechanisms different types ideas targets future treatment identified, limitations field highlighted.
Язык: Английский
Процитировано
0
Cell Death Discovery, Год журнала: 2025, Номер 11(1)
Опубликована: Апрель 29, 2025
Abstract Hepatocellular carcinoma (HCC) is characterized by programmed cell death ligand-1 (PD-L1)-mediated immune escape. This study aimed to elucidate the function and mechanism behind KIAA1429, a component of N6-methyladenosine (m 6 A) complex, in escape HCC. PD-L1 expression was assessed through immunofluorescence staining, flow cytometry used determine CD8 + T percentage. The level IFN-γ detected using enzyme-linked immunosorbent assay. Cell proliferation, migration, invasion were evaluated CCK-8, colony formation, Transwell assays, respectively. m A modification measured an RNA methylation quantification assay, dot blot, methylated immunoprecipitation-qPCR. Molecule interaction validated pulldown, immunoprecipitation, chromatin co-immunoprecipitation assays. In vivo HCC growth NOD/SCID mice. We found that TIP60, KIAA1429 KDM5B highly expressed cells, while FoxO1 poorly expressed. Functionally, TIP60/KIAA1429 silencing inhibited PD-L1-mediated evasion, growth, invasion. Mechanistically, TIP60 led acetylation which promoted A-YTHDF1-dependent manner, subsequently restrained transcription FoxO1. Enforcing YTHDF1 or depleting markedly reversed suppressive effect shKIAA1429 on Overall, these findings suggest acetylated KIAA1429-mediated endows cells with evasion regulation KDM5B/FoxO1 axis, provide treatment option for targeting KIAA1429.
Язык: Английский
Процитировано
0
Biomolecules, Год журнала: 2024, Номер 14(10), С. 1319 - 1319
Опубликована: Окт. 17, 2024
N6-methyladenosine (m
Процитировано
0