Evidence map›Paper›PMID 41436732›Full record

ArticleCell death & disease2025

NSUN2 mediated-aberrant 5-methylcytosine methylation regulates autophagy-related ferroptosis in oral squamous cell carcinoma progression.

Yunyang Lu, Runze Li, Weidong Du, Jie Wu, Yi He, Lingyu Yuan, Xun Chen, Shiyu Lv, Fangyang Shi, Jiajun Hu and 2 more

Abstract read
In one paragraph

Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yunyang Lu *Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Runze Li *Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Weidong Du *Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Jie WuHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Yi HeHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Lingyu YuanDepartment of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Xun ChenHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Shiyu LvHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Fangyang ShiHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Jiajun HuHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Wei ZhaoHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China. zhaowei3@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0003-0251-8084
Dongsheng YuHospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China. yudsh@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-2176-9308

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82373255Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation) 2024A1515012918
6 · The paper itself

Abstract

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastasis rates and poor prognosis. This study investigated the role of NOP2/Sun RNA methyltransferase family member 2 (NSUN2), a key 5-methylcytosine (m5C) methyltransferase, and m5C methylation in the progression of OSCC, particularly in relation to ferroptosis resistance. NSUN2 is significantly overexpressed in OSCC tissues and cell lines and its high expression correlates with poor prognosis and aggressive tumor characteristics. Knockdown of NSUN2 in ferroptosis-resistant OSCC cells resulted in increased sensitivity to ferroptosis. Conversely, NSUN2 overexpression conferred ferroptosis resistance, reducing iron accumulation and restoring GPX4 expression even under erastin treatment. Mechanistically, NSUN2 mediates m⁵C modification of sequestosome 1 (SQSTM1)/P62 mRNA, and the m5C reader protein Y-box binding protein 1 (YBX1) enhances SQSTM1/P62 mRNA stability. This regulation suppresses autophagy and thereby inhibits autophagy-dependent ferroptosis in OSCC. In vivo xenograft models confirmed that NSUN2 knockdown significantly inhibited tumorigenicity. Notably, treatment with an autophagy inhibitor (3-MA) or a ferroptosis inhibitor (Fer-1) partially restored tumor growth in NSUN2-knockdown cells, validating the critical role of autophagy and ferroptosis in NSUN2-mediated OSCC progression. These findings identify the NSUN2-YBX1-SQSTM1/P62 axis as a key regulator of autophagy-dependent ferroptosis in OSCC, highlighting NSUN2 as a promising epitranscriptomic target to enhance ferroptosis induction for OSCC therapy.

Indexed as

5-MethylcytosineAutophagyCarcinoma, Squamous CellFerroptosisMethyltransferasesMouth NeoplasmsAnimalsCell Line, TumorDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansMaleMethylationMiceMice, Inbred BALB C5-MethylcytosineMethyltransferasesNSUN2 protein, humanSequestosome-1 ProteinSQSTM1 protein, humanY-Box-Binding Protein 1YBX1 protein, human

Identifiers

PMID41436732
PMCPMC12728175

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.