NAT10-mediated RNA acetylation enhances HNRNPUL1 mRNA stability to contribute cervical cancer progression.

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N-acetyltransferase10(NAT10) acts as an enzyme that regulates mRNA acetylation modifications. Currently, the role of NAT10-mediated RNA acetylation modification in cervical cancer remains to be elucidated. On the basis of transcriptome analysis of TCGA and GEO open datasets (GSE52904, GSE29570, GSE122697), NAT10 is upregulated in cervical cancer tissues and correlated with poor prognosis. Knockdown of NAT10 suppressed the cell proliferation, invasion, and migration of cervical cancer cells. The in vivo oncogenic function of NAT10 was also confirmed in xenograft models. Combined RNA-seq and acRIP-seq analysis revealed HNRNPUL1 as the target of NAT10 in cervical cancer. NAT10 positively regulate HNRNPUL1 expression by promoting ac4C modification and stability of HNRNPUL1 mRNA. Furthermore, depletion of HNRNPUL1 suppressed the cell division, invasion, and migration of cervical cancer. HNRNPUL1 overexpression partially restored cellular function in cervical cancer cells with NAT10 knockdown. Thus, this study demonstrates that NAT10 contributes to cervical cancer progression by enhancing HNRNPUL1 mRNA stability via ac4C modification, and NAT10-ac4C-HNRNPUL1 axis might be a potential target for cervical cancer therapy.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier survival analysis from the GEPIA data analysis platform showed that cervical cancer patients with high NAT10 expression had poorer Disease-free survival (DFS) compared to cervical cancer patients with low NAT10 expression, indicating that NAT10 expression was negatively associated with DFS for cervical cancer patients (Fig. 1E).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37484809", "locator": "sections[17] \"3.1. 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Combined RNA-seq and acRIP-seq analysis revealed HNRNPUL1 as", "er remains to be elucidated. On the basis of transcriptome analysis of TCGA and GEO open datasets (GSE5"], "order_basis": "paper_text_order:412", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tissues and correlated with poor prognosis. Knockdown of NAT10 suppressed the cell proliferation,", "function in cervical cancer cells with NAT10 knockdown. Thus, this study demonstrates that NAT10 co"], "order_basis": "paper_text_order:583", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["and migration of cervical cancer cells. The in vivo oncogenic function of NAT10 was also confirm"], "order_basis": "paper_text_order:691", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d Methods 2.1 Cell Culture Cell lines (SiHa, Hela and HEK293T) were obtained from Cell Line Re", "d DMEM (GIBCO, USA) was used for HEK293T and Hela cells. The culture mediums were supplemented"], "order_basis": "paper_text_order:1483", "id": "assay:4"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Kaplan-Meier survival analysis from the GEPIA data analysis platform showed that cervical cancer patients with high NAT10 expression had poorer Disease-free survival (DFS) compared to cervical cancer patients with low NAT10 expression, indicating that NAT10 expression was negatively associated with DFS for cervical cancer patients (Fig. 1E)."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}