Evidence map›Paper›PMID 37865189›Full record

ArticleJournal of advanced research2024

Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.

Xiaomin Chen, Tiange Lu, Mengfei Ding, Yiqing Cai, Zhuoya Yu, Xiangxiang Zhou, Xin Wang

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
4.5field-weighted citation impact, top 5% of its field
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

35 citing papers in PubMed, 29 citations in OpenAlex.

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  13. mFrontiers in cell and developmental biology · 2026
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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

7 authors at 2 institutions in 1 country.

Xiaomin ChenDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
Tiange LuDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
Mengfei DingDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
Yiqing CaiDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
Zhuoya YuDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China.
Xiangxiang ZhouDepartment of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 251006, China. Electronic address: xiangxiangzhou@sdu.edu.cn.
Xin WangDepartment of Hematology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, China; Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China; Branch of National Clinical Research Center for Hematologic Diseases, Jinan, Shandong 250021, China; National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, Suzhou 251006, China. Electronic address: xinw007@126.com.
Shandong University · CNSoochow University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEpigenetic alterations play crucial roles in diffuse large B-cell lymphoma (DLBCL). Disturbances in lipid metabolism contribute to tumor progression. However, studies in epigenetics, especially its critical regulator YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), on lipid metabolism regulation in DLBCL are unidentified.

objectivesElucidate the prognostic value and biological functions of YTHDF2 in DLBCL and illuminate the underlying epigenetic regulation mechanism of lipid metabolism by YTHDF2 in DLBCL development.

methodsThe expression and clinical value of YTHDF2 in DLBCL were performed in public databases and clinical specimens. The biological functions of YTHDF2 in DLBCL were determined in vivo and in vitro through overexpression and CRISPR/Cas9-mediated knockout of YTHDF2. RNA sequencing, lipidomics, methylated RNA immunoprecipitation sequencing, RNA immunoprecipitation-qPCR, luciferase activity assay, and RNA stability experiments were used to explore the potential mechanism by which YTHDF2 contributed to DLBCL progression.

resultsYTHDF2 was highly expressed in DLBCL, and related to poor prognosis. YTHDF2 overexpression exerted a tumor-promoting effect in DLBCL, and knockdown of YTHDF2 restricted DLBCL cell proliferation, arrested cell cycle in the G2/M phase, facilitated apoptosis, and enhanced drug sensitivity to ibrutinib and venetoclax. In addition, YTHDF2 knockout drastically suppressed tumor growth in xenograft DLBCL models. Furthermore, a regulatory role of YTHDF2 in ceramide metabolism was identified in DLBCL cells. Exogenous ceramide effectively inhibited the malignant phenotype of DLBCL cells in vitro. The binding of YTHDF2 to m6A sites on alkaline ceramidase 2 (ACER2) mRNA promoted its stability and expression. Enhanced ACER2 expression hydrolyzed ceramides, disrupting the balance between ceramide and sphingosine-1-phosphate (S1P), activating the ERK and PI3K/AKT pathways, and leading to DLBCL tumorigenesis.

conclusionThis study demonstrated that YTHDF2 contributed to the progression of DLBCL by regulating ACER2-mediated ceramide metabolism in an m6A-dependent manner, providing novel insights into targeted therapies.

Indexed as

CarcinogenesisCeramidesLymphoma, Large B-Cell, DiffuseRNA-Binding ProteinsAlkaline CeramidaseAnimalsApoptosisCell Line, TumorCell ProliferationEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansLipid MetabolismMicePrognosisACER2 protein, humanAlkaline CeramidaseCeramidesRNA-Binding ProteinsYTHDF2 protein, humanACER2CeramideDLBCLTumorigenesisYTHDF2

Identifiers

PMID37865189
PMCPMC11379987
OpenAlexW4387776358

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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 OpenQuestion graph.