NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells

Su, Yongjian; Liu, Jiangrui; Zheng, Zhuo; Shi, Liangpan; Huang, Wen‐Chang; Huang, Xiaohui; Ye, Chengwei; Jing, Qi; Wang, Weidong; Zhuang, Haibin

doi:10.1007/s12013-023-01152-1

Cited by 6 publications

(2 citation statements)

References 28 publications

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“…Over the past decade, the oncogenic role of NSUN5 has been identified in several cancer types. In gastric cancer, NSUN5 modulates ferritin heavy chain 1 and inhibits ferroptosis, ultimately enhancing tumor cell proliferation [ 13 ]. In clear-cell renal cell carcinoma, NSUN5 overexpression facilitates cancer cell invasion, proliferation, and migration while also inhibiting apoptosis by suppressing the p53 signaling pathway [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism

Gu,

Li,

Gao

et al. 2024

Oncogene

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Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer-related mortality worldwide. Nop2/Sun domain family member 5 (NSUN5), a conserved RNA 5-methylcytosine methyltransferase, is conventionally recognized as oncogenic. However, its role in HCC development remains unknown. In this study, we observed a remarkable upregulation of NSUN5 expression in both tumor tissues from patients with HCC, establishing a correlation with unfavorable clinical outcomes. NSUN5 knockdown and overexpression significantly inhibited and promoted HCC cell proliferation, respectively. Additionally, employing a combination of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RIP-seq techniques, we identified zinc finger BED domain-containing protein 3 (ZBED3) as a novel downstream target of NSUN5. Additionally, we found that the overexpression of ZBED3 counteracted the tumor-suppressing effect of NSUN5 knockdown and simultaneously reversed the inhibition of the Wnt/β-catenin signaling pathway. In summary, we elucidated the oncogenic role of NSUN5 in HCC development and identified the ZBED3/Wnt/β-catenin signaling pathway as its downstream target. This study provides a novel therapeutic target for further development in HCC treatment.

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Section: Introductionmentioning

confidence: 99%

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism

Gu,

Li,

Gao

et al. 2024

Oncogene

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“…Studies have found that NSUN5 acts as a ribosomal RNA methyltransferase to regulate global protein synthesis and normal growth [10]. NSUN5 also promotes progression and predicts poor prognosis in hepatocellular cancer and gastric cancer [11,12]. NSUN5-mediated m5C modi cation of GPX4 facilitated anticancer immunity in colon adenocarcinoma [13].…”

Section: Introductionmentioning

confidence: 99%

The Oncogenic and Prognostic Significance of NSUN5 in Pan-Cancer and Its Potential roles in Clear Renal Cell Carcinoma

CHAN,

Luo,

Wen

et al. 2024

Preprint

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Background: NSUN5, belonging to the NOL1/NOP2/SUN domain (NSUN) family, is implicated in RNA stabilization and widely expressed in different tumor types. Nevertheless, its precise role in pan-cancer, particularly its involvement in immunotherapy, remains poorly understood. Methods: The publicly available databases and the vitro experiments were used to investigate the roles of NSUN5 in human tumors. CellMiner database and Checkmate-025 cohort analyzed the sensitivity of NSUN5 with various drugs, particularly in PD-1 inhibitor. Subsequently, we constructed models to predict prognosis based on the expression of NSUN5 in kidney renal clear cell carcinoma (KIRC), glioma (GBM) and hepatocellular carcinoma (LIHC) cohorts. We further investigate the association between NSUN5 expression levels and immune cell infiltration. Gene Set Enrichment Analysis (GSEA) was used to identify the potential pathways with NSUN5 expression. Results: Differential analysis revealed that 18 types of tumors expressed NSUN5 to a greater extent than normal tissues. An easy-to use nomogram based on NSUN5 and several clinicopathological factors can excellently predict the prognosis of patients with GBM, KIRC, and LIHC. In addition, NSUN5 over-expression was positively correlated with exhausted CD8+ T cells and Tregs. Particularly, KIRC patients with heightened NSUN5 expression who underwent PD-1 inhibitor exhibited a poorer prognosis. In vitro results showed that NSUN5 down-expression promoted tumor cell senescence while hindered cell proliferation and migration. Conclusion: These findings inferred that NSUN5 acts as a prognostic factor to predict the OS in multiple types of tumors and implied the importance of developing novel immunotherapeutic strategies.

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The prognostic implications and oncogenic role of NSUN5 in clear cell renal cell carcinoma

Huang,

Luo,

Wen

et al. 2024

Clin Exp Med

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Clear cell renal cell carcinoma (ccRCC), a predominant form of urinary malignancy, requires the identification of reliable biomarkers to enhance both prognostic outcomes and therapeutic developments specific to ccRCC. NSUN5, a member of the NOL1/NOP2/SUN domain (NSUN) family, plays a critical role in RNA stabilization and exhibits widespread expression across various tumor types. However, the exact function of NSUN5 in ccRCC remains insufficiently understood. Data were collated from cohorts of ccRCC patients who underwent nephrectomy, including those from the Cancer Genome Atlas (TCGA) and the Sun Yat-sen University Cancer Center (SYSUCC), to evaluate the clinical relevance of NSUN5. Integrative models based on NSUN5 expression were subsequently developed to predict the prognosis of ccRCC within the TCGA and SYSUCC cohorts. Furthermore, the impact of NSUN5 on RCC cells and its association with cellular senescence were corroborated through in vitro experimental analyses. NSUN5 exhibited elevated expression in both ccRCC patients and renal cancer cell lines, whose upregulation significantly correlated with age, tumor size, TNM stage, WHO/International Society of Urological Pathology (ISUP) grade, presence of necrosis, and a poor prognosis. An accessible nomogram, incorporating NSUN5 along with various clinicopathological parameters, was adept at predicting outcomes for ccRCC patients. Additionally, in vitro findings indicated that reduced expression of NSUN5 enhanced tumor cell senescence and simultaneously inhibiting cell proliferation and migration. These observations suggest that elevated NSUN5 expression is linked to poorer overall survival (OS) and progression-free survival (PFS), positioning NSUN5 as a viable diagnostic and prognostic biomarker in ccRCC. Supplementary Information The online version contains supplementary material available at 10.1007/s10238-024-01507-9.

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NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells

Cited by 6 publications

References 28 publications

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism

RNA 5-methylcytosine writer NSUN5 promotes hepatocellular carcinoma cell proliferation via a ZBED3-dependent mechanism

The Oncogenic and Prognostic Significance of NSUN5 in Pan-Cancer and Its Potential roles in Clear Renal Cell Carcinoma

The prognostic implications and oncogenic role of NSUN5 in clear cell renal cell carcinoma

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