The Journal of Steroid Biochemistry and Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 106767 - 106767
Published: April 1, 2025
Language: Английский
Advanced Science, Journal Year: 2023, Volume and Issue: 10(32)
Published: Oct. 11, 2023
Immunotherapy has recently emerged as the predominant therapeutic approach for cervical cancer (CCa), driven by groundbreaking clinical achievements of immune checkpoint inhibitors (ICIs), such anti-PD-1/PD-L1 antibodies. N4-acetylcytidine (ac4C) modification, catalyzed NAT10, is an important posttranscriptional modification mRNA in cancers. However, its impact on immunological dysregulation and tumor immunotherapy response CCa remains enigmatic. Here, a significant increase NAT10 expression tissues initially observed that clinically associated with poor prognosis. Subsequently, it found HOXC8 activated binding to promoter, thereby stimulating ac4C FOXP1 enhancing translation efficiency, eventually leading induction GLUT4 KHK expression. Moreover, NAT10/ac4C/FOXP1 axis activity resulted increased glycolysis continuous lactic acid secretion cells. The acid-enriched microenvironment (TME) further contributed amplifying immunosuppressive properties tumor-infiltrating regulatory T cells (Tregs). Impressively, knockdown enhanced efficacy PD-L1 blockade-mediated regression vivo. Taken together, findings revealed oncogenic role initiating crosstalk between cell immunosuppression, which can be target synergistic PD-1/PD-L1 blockade CCa.
Language: Английский
Citations
42
Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)
Published: Aug. 19, 2024
Drug resistance remains a significant challenge in cancer treatment. Recently, the interactions among various cell types within tumor microenvironment (TME) have deepened our understanding of mechanisms behind treatment resistance. Therefore, this review aims to synthesize current research focusing on infiltrating cells and drug suggesting that targeting TME could be viable strategy combat issue. Numerous factors, including inflammation, metabolism, senescence, hypoxia, angiogenesis, contribute Overexpression STAT3 is commonly associated with drug-resistant or stromal cells. Current often generalizes impact resistance, lacking specificity statistical robustness. Thus, future should take notice issue aim provide high-quality evidence. Despite existing limitations, overcome therapy hold promising valuable potential.
Language: Английский
Citations
11
Theranostics, Journal Year: 2025, Volume and Issue: 15(6), P. 2428 - 2450
Published: Jan. 20, 2025
Rationale: Abnormal metabolic states contribute to a variety of diseases, including cancer. RNA modifications have diverse biological functions and are implicated in cancer development, gastric (GC). However, the direct relationship between glucose homeostasis 4-acetylcytosine (ac4C) modification GC remains unclear. Methods: The prognostic value acetyltransferase NAT10 expression was evaluated human cohort. Additionally, preoperative PET/CT data from patients Micro-PET/CT imaging mice were employed assess metabolism. role investigated through various experiments, xenografts, organoids, conditional knockout (cKO) mouse model. underlying mechanisms examined using dot blotting, immunofluorescence staining, co-immunoprecipitation, high-throughput sequencing, among other techniques. Results: Glucose deprivation activates autophagy-lysosome pathway, leading degradation by enhancing its interaction with sequestosome 1 (SQSTM1)/microtubule-associated protein light chain 3 alpha (LC3) complex, ultimately resulting reduction ac4C modification. Furthermore, levels elevated tissues correlate poor prognosis. A strong correlation exists 18F-FDG uptake patients. drives glycolytic metabolism carcinogenesis vitro vivo. Mechanistically, stimulates at intersection coding sequence (CDS) 3' untranslated region (3'UTR) hexokinase 2 (HK2) mRNA, stability activating thereby driving tumorigenesis. Conclusion: Our findings highlight critical crosstalk epitranscriptome carcinogenesis. This finding offers potential strategy targeting NAT10/HK2 axis for treatment patients, especially those highly active
Language: Английский
Citations
1
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
Oncogene, Journal Year: 2024, Volume and Issue: 43(15), P. 1077 - 1086
Published: Feb. 26, 2024
Language: Английский
Citations
5
International Immunopharmacology, Journal Year: 2024, Volume and Issue: 133, P. 112124 - 112124
Published: April 24, 2024
Language: Английский
Citations
5
Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)
Published: Sept. 9, 2024
Language: Английский
Citations
5
Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)
Published: Oct. 4, 2024
Language: Английский
Citations
5
Cancers, Journal Year: 2023, Volume and Issue: 15(24), P. 5795 - 5795
Published: Dec. 11, 2023
Tumor-associated macrophages (TAMs) play a pivotal role in shaping the tumor microenvironment. Lactic acid (LA) has been identified as an influential factor promoting immune escape and progression. However, mechanisms through which LA modulates TAMs colorectal cancer (CRC) remain poorly understood. We used qRT-PCR to quantify expression of LA-related genes (LDHA LAMP2) CRC tissues adjacent nontumor (n = 64). The biological effects on tumors were evaluated via qRT-PCR, Western blot, RNA-seq, wound healing assay, colony formation assay vitro, allograft mouse models vivo. found LDHA LAMP2 was highly elevated regions positively associated with poor clinical stage CRC. A high concentration generated under hypoxia; it could promote progression metastasis involvement macrophages. inhibition release impaired this protumor phenomenon. Mechanically, induced M2 AKT/ERK signaling pathway; subsequently, secreted CCL8 facilitated proliferation cells by activating CCL8/CCR5/mTORC1 axis. This effect inhibited antagonist or knockdown CCR5. In conclusion, lactate-induced accelerated
Language: Английский
Citations
12
Oncogene, Journal Year: 2024, Volume and Issue: 43(48), P. 3498 - 3516
Published: Oct. 10, 2024
Language: Английский
Citations
4