Affinage

YTHDF2

YTH domain-containing family protein 2 · UniProt Q9Y5A9

Length
579 aa
Mass
62.3 kDa
Annotated
2026-06-11
100 papers in source corpus 60 papers cited in narrative 60 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YTHDF2 is a cytoplasmic m6A reader that recognizes N6-methyladenosine marks on target mRNAs through its YTH domain and primarily routes those transcripts to deadenylation-dependent decay, thereby tuning the abundance of methylated transcripts across cell-cycle, developmental, and immune programs (PMID:32267835, PMID:32905781, PMID:34216543). Substrate recognition depends on a conserved hydrophobic pocket (Trp432), which also mediates lower-affinity binding to m5C-modified RNA (PMID:31815440), and decay is executed by recruitment of the CCR4-NOT deadenylase complex (PMID:32905781). Through m6A-dependent turnover of specific substrates YTHDF2 drives mitotic entry by degrading WEE1 (PMID:32267835), maintains hematopoietic and neural stem-cell pools by clearing inflammation- and TGF-β/JAK-STAT-related transcripts (PMID:29855337, PMID:33156926, PMID:39476834), and governs spermatogenesis, cardiac homeostasis, and postnatal muscle growth by destabilizing matrix, hypertrophic, and anti-growth regulators such as Myzap, eEF2, and ASB2 (PMID:37315764, PMID:37791304, PMID:38467649). Across immune lineages YTHDF2 reshapes NF-κB and interferon signaling—degrading negative regulators of NF-κB in MDSCs and Tregs and innate-immune transcripts such as RIG-I and CXCL10 to promote immune evasion—while being required for NK-cell maturation and germinal-center B-cell fate (PMID:34160549, PMID:35508130, PMID:37236197, PMID:37345898, PMID:36939388, PMID:37129929). Beyond decay, YTHDF2 stabilizes select transcripts and promotes translation: it recruits eIF3B, or an eIF3F/DDX1 complex, or PABPC1 to enhance translation of methylated mRNAs, and as a dual m6A/m5C reader it can stabilize m5C-modified messages while degrading m6A targets (PMID:38247171, PMID:39694037, PMID:40480228). It additionally acts independently of m6A, promoting aggresome formation through a UPF1-containing misfolded-polypeptide/dynein complex (PMID:37803021) and entering the nucleus to support nascent transcription via IKZF1/3 (PMID:39500904). YTHDF2 protein abundance is itself heavily regulated—stabilized by CDK1-dependent phosphorylation, EGFR/SRC/ERK phosphorylation, OGT-mediated O-GlcNAcylation at Ser263, HSP90β-mediated protection from STUB1, and OTUB1 deubiquitination, and degraded via CUL1/CUL4A/DDB1/SKP2 ubiquitin ligases or autophagy (PMID:32267835, PMID:33420027, PMID:36765030, PMID:37515378, PMID:38462165, PMID:38516932).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2018 Medium

    Established that YTHDF2 directly binds m6A sites in target-mRNA UTRs and drives their degradation, providing the first functional substrate evidence in a cancer context.

    Evidence RIP and mRNA stability assays with loss/gain-of-function on EGFR mRNA in HCC cells

    PMID:30423408

    Open questions at the time
    • Single substrate, single lab
    • Did not define the decay machinery recruited
  2. 2019 High

    Defined YTHDF2 as a transcriptome-wide destabilizer of m6A-modified mRNAs required for leukemic stem cell propagation but dispensable for normal HSCs, establishing a therapeutic window.

    Evidence Conditional KO mouse and human AML models with mRNA half-life and m6A-seq

    PMID:31031138

    Open questions at the time
    • Mechanism of selective LSC dependence not fully resolved
    • Decay machinery not mapped here
  3. 2019 High

    Showed the YTH-domain residue Trp432 that reads m6A also recognizes m5C, broadening YTHDF2 to a dual-mark reader and linking it to rRNA processing.

    Evidence Quantitative pulldown, in vitro binding with Trp432 mutagenesis, CRISPR KO with bisulfite sequencing

    PMID:31815440

    Open questions at the time
    • m5C binding affinity lower than m6A; physiological weight unclear
    • Mechanism connecting YTHDF2 to pre-rRNA processing undefined
  4. 2020 High

    Identified the effector machinery: YTHDF2 recruits the CCR4-NOT deadenylase complex to clear methylated transcripts, and is degraded via specific cullin-based E3 ligases, placing it in a CDK1-WEE1 mitotic feedforward loop.

    Evidence Reciprocal co-IP of CCR4-NOT, KO/rescue, CDK1 inhibitor, mRNA stability assays in iPSC reprogramming and HeLa

    PMID:32267835 PMID:32905781

    Open questions at the time
    • Structural basis of CCR4-NOT recruitment not defined
    • Determinants choosing decay vs stabilization unknown
  5. 2021 High

    Demonstrated YTHDF2 protein abundance is gated by post-translational modification—EGFR/SRC/ERK phosphorylation and OGT O-GlcNAcylation at Ser263 stabilize it—coupling oncogenic signaling to reader activity.

    Evidence Phospho/O-GlcNAc site identification by MS and mutagenesis, ubiquitination and mRNA-stability assays in GBM and HCC

    PMID:33420027 PMID:36765030

    Open questions at the time
    • How each PTM alters substrate selection not dissected
    • Crosstalk among the modifications unresolved
  6. 2021 High

    Established YTHDF2 as a stem-cell and developmental regulator: it maintains neural and hematopoietic stem cells by degrading inflammation- and JAK-STAT-related transcripts, with embryonic lethality on loss.

    Evidence Conditional/hematopoiesis-specific KO mice, serial transplantation, m6A methylome and mRNA stability assays

    PMID:29855337 PMID:33156926

    Open questions at the time
    • Tissue-specific substrate sets only partially enumerated
    • Distinction between cell-intrinsic and niche effects incomplete
  7. 2021 High

    Revealed YTHDF2 buffers transcriptome output in MYC-driven and TNBC tumors, where its decay activity counteracts elevated mRNA synthesis and its loss triggers ER-stress apoptosis.

    Evidence Pooled CRISPR screen, eCLIP, m6A-seq, scRibo-STAMP, xenografts

    PMID:34216543

    Open questions at the time
    • Generality of the buffering role across tumor types untested here
    • Translation vs decay contribution not separated
  8. 2021 Medium

    Uncovered non-canonical and translation-promoting roles: heat-shock-induced nuclear translocation via the YTH domain, and PBRM1-dependent enhancement of HIF-1α translation, showing YTHDF2 is not solely a decay factor.

    Evidence Deletion-mutant localization imaging, co-IP, RIP, polysome profiling

    PMID:34200988 PMID:34671198

    Open questions at the time
    • Nuclear function mechanism incompletely defined
    • Switch between decay and translation promotion unclear
  9. 2022 High

    Showed YTHDF2 protein is protected from STUB1-mediated degradation by HSP90β, and can paradoxically stabilize substrate mRNAs (ACER2), extending its regulatory repertoire beyond decay.

    Evidence Reciprocal co-IP with domain mapping, ubiquitination assays, MeRIP and stability assays in HCC and DLBCL

    PMID:37515378 PMID:37865189

    Open questions at the time
    • Rules governing stabilization vs decay of a given transcript unknown
    • Whether HSP90β chaperoning affects substrate selection untested
  10. 2023 High

    Established YTHDF2 as a central node in tumor immune evasion across myeloid, T-regulatory, NK, and innate-sensing pathways, frequently by degrading NF-κB negative regulators or innate-immune transcripts (RIG-I, CXCL10).

    Evidence Lineage-specific conditional KO mice, m6A-dependent decay assays, in vivo tumor/irradiation models

    PMID:36658237 PMID:36939388 PMID:37129929 PMID:37236197 PMID:37345898

    Open questions at the time
    • Why YTHDF2 selects NF-κB-regulatory substrates is unresolved
    • Context-dependent pro- vs anti-inflammatory outputs not unified
  11. 2023 High

    Demonstrated m6A-independent activities: YTHDF2 promotes aggresome formation through a UPF1/dynein misfolded-polypeptide complex and enters the nucleus to support transcription via IKZF1/3, plus autoregulating its own mRNA.

    Evidence Co-IP of complex components, dynein-interaction and live-cell aggresome imaging, conditional T-cell KO with chromatin assays

    PMID:37803021 PMID:39500904

    Open questions at the time
    • Structural basis of m6A-independent protein interactions undefined
    • Balance between nuclear and cytoplasmic pools unclear
  12. 2023 Medium

    Extended YTHDF2's physiological role to cardiac and pulmonary homeostasis through mRNA-stability control of eEF2, Myzap, and Hmox1, with tissue-specific decay or stabilization outcomes.

    Evidence Cardiomyocyte- and myeloid-specific KO mice, Ribo-seq, proteomics, RIP and stability assays, pharmacological epistasis

    PMID:36801705 PMID:37315764 PMID:37791304

    Open questions at the time
    • Why some substrates are stabilized rather than degraded in these tissues unresolved
    • Upstream signals controlling cardiac YTHDF2 only partly defined
  13. 2024 High

    Resolved YTHDF2 as a dual m6A/m5C reader with opposing transcript fates—stabilizing m5C mRNAs via PABPC1 to boost translation while degrading m6A targets—and showed its overexpression alone transforms B cells.

    Evidence In vitro reader assays, PABPC1 co-IP, translation/stability assays, overexpression-driven transformation model, small-molecule inhibitor

    PMID:39694037

    Open questions at the time
    • How a single reader partitions m5C vs m6A substrates mechanistically unknown
    • In vivo contribution of m5C reading versus m6A decay not separated
  14. 2024 High

    Mapped additional layers of YTHDF2 protein control—OTUB1 and USP10 deubiquitination, lncRNA JPX-mediated destabilization, and IFN-γ/FMDV-VP1-driven autophagic degradation—linking its turnover to immune and viral contexts.

    Evidence In vitro ubiquitination assays, co-IP, RNA pulldown, autophagy modulation, conditional KO tumor models

    PMID:38441563 PMID:38462165 PMID:38516932 PMID:38820140

    Open questions at the time
    • Hierarchy among competing stabilizing/destabilizing inputs unknown
    • Whether autophagic and proteasomal routes dominate in specific tissues unclear
  15. 2025 High

    Defined a discrete translation-enhancing complex (YTHDF2-eIF3F-DDX1) acting independently of decay, and validated YTH-domain-targeting small molecules that disrupt m6A binding, advancing YTHDF2 as a druggable target.

    Evidence Co-IP, stability-vs-translation comparison, eCLIP, structure-guided/phenylpyrazole inhibitor binding to the YTH pocket, apoptosis assays

    PMID:40017738 PMID:40480228

    Open questions at the time
    • No reported full crystal structure of inhibitor-bound YTH domain
    • Determinants directing YTHDF2 to translation vs decay complexes unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central unresolved question is what molecular switch dictates whether YTHDF2 destabilizes, stabilizes, or promotes translation of a given m6A/m5C transcript, and how its many PTMs and protein partners are integrated to set that outcome in a tissue-specific manner.
  • No unified model linking PTM state, partner choice, and transcript fate
  • Structural basis of m6A-independent functions undefined
  • Relative in vivo weight of decay vs translation vs nuclear roles unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0045182 translation regulator activity 3 GO:0060090 molecular adaptor activity 3 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2
Pathway
R-HSA-168256 Immune System 6 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3
Partners
DDX1EIF3BEIF3FHSP90B1OTUB1PABPC1STUB1UPF1
Complex memberships
CCR4-NOT deadenylase complexYTHDF2-eIF3F-DDX1 translation complexmisfolded-polypeptide/aggresome complex (UPF1, CTIF, eEF1A1, DCTN1)

Evidence

Reading pass · 60 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 YTHDF2 directly binds the m6A modification site in the 3'-UTR of EGFR mRNA and promotes its degradation, suppressing cell proliferation in hepatocellular carcinoma cells. RIP assay, mRNA stability assay, loss-of-function/gain-of-function in HCC cells Cancer letters Medium 30423408
2019 YTHDF2 decreases the half-life of diverse m6A-modified transcripts in leukemic stem cells (LSCs), including Tnfrsf2, whose upregulation upon YTHDF2 deficiency primes LSCs for apoptosis; YTHDF2 is required for AML disease initiation and propagation but is not essential for normal HSC function. Mouse/human AML models, conditional KO, mRNA half-life assay, m6A sequencing Cell stem cell High 31031138
2019 YTHDF2 promotes decay of m6A-containing IL11 and SERPINE2 mRNAs; its transcription is suppressed by HIF-2α, creating a feedback loop whereby HIF-2α reduction of YTHDF2 leads to inflammation and vascular abnormalization in hepatocellular carcinoma. m6A-IP sequencing, mRNA stability assay, HIF-2α antagonist treatment, KO mouse model Molecular cancer Medium 31735169
2019 YTHDF2 binds 5-methylcytosine (m5C) in RNA via Trp432 (the same conserved hydrophobic pocket residue required for m6A recognition), albeit with lower affinity than m6A; YTHDF2 knockout increases m5C levels at the majority of rRNA sites and impairs pre-rRNA processing. Quantitative proteomics pull-down, in vitro binding assay with Trp432 mutagenesis, CRISPR-Cas9 KO, RNA bisulfite sequencing Analytical chemistry High 31815440
2019 YTHDF2 depletion in LPS-stimulated macrophages increases the stability of MAP2K4 and MAP4K4 mRNAs, activating MAPK and NF-κB signaling and promoting proinflammatory cytokine expression. YTHDF2 knockdown in RAW264.7 cells, mRNA stability assay, inhibitor rescue experiments International journal of molecular sciences Medium 30875984
2020 YTHDF2 promotes mitotic entry by facilitating m6A-dependent decay of WEE1 mRNA; CDK1 activity stabilizes YTHDF2 protein, forming a CDK1-YTHDF2-WEE1 feedforward loop. YTHDF2 proteolysis is mediated by CUL1, CUL4A, DDB1, and SKP2 E3 ubiquitin ligase complexes. YTHDF2 depletion in HeLa cells, mRNA stability assay, CDK1 inhibitor treatment, identification of E3 ubiquitin ligase components by co-IP PLoS biology High 32267835
2020 YTHDF2 recruits the CCR4-NOT deadenylase complex to mediate mRNA deadenylation and clearance of m6A-modified somatic gene transcripts (including Tead2 and Tgfb1) during somatic reprogramming to iPSCs; YTHDF3 independently recruits PAN2-PAN3 deadenylase complex for the same purpose. Ythdf2/3 knockout, mRNA clearance assays, co-IP of CCR4-NOT and PAN2-PAN3, rescue experiments Cell reports High 32905781
2020 YTHDF2 knockdown in mouse spermatogonia causes decreased expression of MMP3, MMP13, ADAMTS1, and ADAMTS9, affecting cell-matrix adhesion and proliferation; m6A-IP-PCR and RIP-PCR confirmed these transcripts are m6A-modified and directly bound by YTHDF2. CRISPR/Cas9 KO, m6A-IP-PCR, RIP-PCR, mRNA stability assay, inhibitor rescue Cell death & disease Medium 31959747
2021 EGFR/SRC/ERK signaling phosphorylates YTHDF2 at serine 39 and threonine 381, stabilizing the YTHDF2 protein; YTHDF2 in turn facilitates m6A-dependent mRNA decay of LXRA and HIVEP2 to promote GBM tumorigenesis and inhibits LXRα-dependent cholesterol homeostasis. Phosphorylation site identification by mutagenesis, mRNA decay assay, co-IP, YTHDF2 KD/OE in GBM cells and xenografts Nature communications High 33420027
2021 Histone lactylation drives YTHDF2 expression; YTHDF2 then recognizes m6A-modified PER1 and TP53 mRNAs and promotes their degradation to accelerate tumorigenesis in ocular melanoma. Histone lactylation profiling, RIP assay, mRNA stability assay, in vitro and in vivo KD/OE Genome biology Medium 33726814
2021 Conditional depletion of Ythdf2 in mice causes embryonic lethality with compromised neural development; Ythdf2 loss impairs NSPC self-renewal and differentiation, and delays degradation of m6A-containing neural development-related mRNAs including JAK-STAT cascade inhibitory genes. Conditional KO mice, m6A methylome profiling of KO NSPCs, mRNA stability assay in vivo/in vitro Genome biology High 29855337
2021 YTHDF2 disruption in triple-negative breast cancer stabilizes MAPK pathway mRNAs (identified by eCLIP and m6A sequencing), increasing global translation rates and inducing EMT; in MYC-driven tumors, YTHDF2-dependent mRNA degradation counteracts the global increase in mRNA synthesis, and YTHDF2 loss triggers ER stress-induced apoptosis. Pooled CRISPR-Cas9 screen, eCLIP, m6A-seq, scRibo-STAMP, xenograft tumors Molecular cell High 34216543
2021 YTHDF2 recognizes m6A modification and promotes mRNA decay of AXIN1 (a negative regulator of Wnt/β-catenin), thereby activating Wnt/β-catenin signaling to promote lung adenocarcinoma cell proliferation and migration; AXIN1 KO rescues the inhibitory effect of YTHDF2 depletion. Integrative RNA-seq, m6A-seq, CLIP-seq, RIP-seq, mRNA stability assay, epistasis rescue experiments Cell death & disease High 33980824
2021 YTHDF2 recognizes m6A-modified Notch1 mRNA in the cytoplasm and promotes its decay, suppressing Notch signaling (HES1, HES5); under heat shock, YTHDF2 translocates to the nucleus via its YTH domain, reducing Notch1 mRNA decay and restoring Notch signaling. YTH domain deletion mutants confirm the domain is critical for both m6A binding and nuclear translocation. YTHDF2 deletion mutant analysis, mRNA stability assay, nuclear translocation imaging, heat shock treatment International journal of biological sciences Medium 34671198
2021 YTHDF2 is required for NK cell terminal maturation and effector function in antitumor/antiviral immunity; YTHDF2 forms a STAT5-YTHDF2 positive feedback loop upon IL-15 stimulation and targets Tardbp mRNA (involved in cell survival/proliferation) for degradation in NK cells. Ythdf2 conditional KO in NK cells, transcriptome-wide YTHDF2 binding screening, in vivo tumor/viral infection models The Journal of experimental medicine Medium 34160549
2021 Ythdf2-deficient hematopoietic stem cells chronically upregulate multiple m6A-modified inflammation-related transcripts, activating proinflammatory pathways; YTHDF2 expression is induced by inflammation and is required to protect HSCs from inflammatory insult. Hematopoiesis-specific Ythdf2 KO mice, serial transplantation, m6A-mRNA abundance profiling The Journal of experimental medicine High 33156926
2021 YTHDF2 recognizes m6A-modified LncRNA FENDRR and promotes its degradation in endometrial cancer cells, thereby elevating SOX4 protein and promoting cell proliferation. RIP assay, mRNA stability assay, knockdown rescue experiments, xenograft model Laboratory investigation Medium 33692441
2021 YTHDF2 promotes AXIN1 mRNA stability and expression in cervical cancer (opposite to its canonical decay function), and AXIN1 knockdown reverses the effects of YTHDF2 depletion on migration, invasion, EMT, and cisplatin sensitivity. MeRIP-seq, actinomycin D mRNA stability assay, epistasis KD rescue experiments Drug development research Medium 35489084
2021 PBRM1 (SWI/SNF component) interacts with YTHDF2 and is required for YTHDF2 binding to m6A-modified HIF-1α mRNA; this interaction promotes HIF-1α mRNA translation, as PBRM1 or YTHDF2 loss reduces HIF-1α protein but not mRNA levels. Co-IP (PBRM1-YTHDF2 interaction), RIP (HIF-1α mRNA binding), polysome profiling, KD experiments Cells Medium 34200988
2021 YTHDF2 depletion in LPS-stimulated osteoclast precursors stabilizes Tnfrsf11a, Traf6, Map4k4, Map2k3, Map2k4, and Nfatc1 mRNAs, enhancing NF-κB and MAPK signaling and promoting inflammatory osteoclastogenesis. Ythdf2 KD in RAW264.7 and BMMs, mRNA stability assay, TRAP/pit formation assays, NF-κB/MAPK inhibitor rescue Cellular signalling Medium 34089814
2021 O-GlcNAc transferase (OGT)-mediated O-GlcNAcylation of YTHDF2 at serine 263 enhances its protein stability by inhibiting its ubiquitination; O-GlcNAcylated YTHDF2 stabilizes MCM2 and MCM5 mRNAs in an m6A-dependent manner to promote cell cycle progression in HBV-related HCC. Mass spectrometry identification of S263 modification, mutagenesis, ubiquitination assay, RIP, m6A-dependent mRNA stability assay Signal transduction and targeted therapy High 36765030
2022 YTHDF2 requires B cell activation to be upregulated; YTHDF2 enhances decay of methylated transcripts encoding key plasmablast-regulating genes to suppress the plasmablast genetic program and promote germinal center B cell fate commitment. Ythdf2 conditional KO in B cells, single-cell RNA-seq, m6A-mRNA decay assay Cell reports Medium 35508130
2022 YTHDF2 promotes CDKN1B mRNA degradation in an m6A-dependent manner in intrahepatic cholangiocarcinoma, driving cell cycle progression and cisplatin resistance. RNA-seq, MeRIP-seq, anti-YTHDF2 RIP-seq, RNA stability assay, PDX model Clinical and translational medicine Medium 35696608
2022 YTHDF2 facilitates m6A-dependent mRNA decay of LXRA and promotes YTHDF2/APC and GSK3β mRNA degradation via Wnt-β-catenin pathway activation in glioblastoma; PRMT6 and CDK9 co-regulate YTHDF2 transcription, with PRMT6 acting upstream. Dual-luciferase reporter assay, ChIP-qPCR, mRNA stability assay, in situ tumor model Journal of experimental & clinical cancer research Medium 38637831
2022 HSP90β physically interacts with YTHDF2 and STUB1 (an E3 ubiquitin ligase) in the cytoplasm; HSP90β inhibits STUB1-induced ubiquitination and degradation of YTHDF2, stabilizing YTHDF2 protein and promoting HCC proliferation and sorafenib resistance. Co-IP, domain mapping (HSP90β large and small middle domain required for interaction), ubiquitination assay, KD/OE experiments Advanced science High 37515378
2022 YTHDF2 binds to m6A sites on ACER2 mRNA and stabilizes (rather than degrades) it, enhancing ACER2 expression; increased ACER2 hydrolyzes ceramides and activates ERK and PI3K/AKT pathways in diffuse large B-cell lymphoma. RNA-seq, lipidomics, MeRIP-seq, RIP-qPCR, RNA stability assay, luciferase assay, CRISPR KO Journal of advanced research Medium 37865189
2022 YTHDF2 accelerates EGR1 mRNA degradation in an m6A-dependent manner in multiple myeloma; EGR1 suppresses proliferation by activating p21cip1/waf1 transcription and inhibiting CDK2-cyclinE1. RIP-PCR, MeRIP-qPCR, mRNA stability assay, EGR1 KD rescue, in vivo xenograft Oncogene Medium 37012388
2022 YTHDF2 degrades STAT5A mRNA at its m6A modification site; reduced STAT5A relieves suppression of MAP2K2 transcription (ChIP-seq), thereby increasing p-ERK and promoting multiple myeloma cell proliferation. m6A-RIP-seq, RIP-PCR, ChIP-seq, mRNA stability assay, YTHDF2 KD/OE Oncogene Medium 35075244
2022 YBX2 physically interacts with YTHDF2 via its cold-shock domain within YBX2-containing cytoplasmic granules; YTHDF2 knockdown ameliorates YBX2-induced HSPA6 mRNA destabilization, demonstrating synergistic effects of YBX2 and YTHDF2 on mRNA stability. Co-IP, transcriptomic analysis, mRNA stability assay, YTHDF2 KD rescue Experimental cell research Medium 37030331
2023 YTHDF2 deficiency in tumor-associated macrophages (TAMs) suppresses tumor growth by reprogramming TAMs toward antitumoral phenotype via targeting IFN-γ-STAT1 signaling; YTHDF2 expression in TAMs is regulated by IL-10-STAT3 signaling. Conditional Ythdf2 KO in macrophages, in vivo tumor models, signaling pathway analysis, siRNA-TLR9 agonist conjugate targeting Nature immunology High 36658237
2023 Ionizing radiation induces YTHDF2 expression via NF-κB signaling; YTHDF2 in turn activates NF-κB by degrading m6A-modified transcripts encoding NF-κB negative regulators, creating an IR-YTHDF2-NF-κB positive feedback circuit that promotes MDSC immunosuppression. Conditional Ythdf2 KO in myeloid cells, mRNA binding/degradation assay, NF-κB signaling analysis, in vivo irradiation tumor models Cancer cell High 37236197
2023 YTHDF2 directly binds and degrades BAMBI transcripts in an m6A-dependent and NF-κB-signaling-dependent manner in MDSCs after ionizing radiation, reducing BAMBI-mediated suppression of TGF-β signaling and extrinsic radioresistance. YTHDF2 RIP assay, m6A-dependent mRNA stability assay, NF-κB signaling inhibition, AAV-BAMBI rescue in tumor models The Journal of clinical investigation Medium 38099498
2023 Loss of YTHDF2 in regulatory T cells (Tregs) leads to increased apoptosis and impaired suppressive function in the tumor microenvironment; elevated TNF signaling in the TME promotes YTHDF2 expression, which then accelerates degradation of m6A-modified NF-κB negative regulator transcripts to activate NF-κB signaling in Tregs. Treg-specific Ythdf2 KO mice, in vivo tumor models, m6A mRNA decay analysis, TNF/NF-κB pathway analysis The EMBO journal High 37345898
2023 YTHDF2 recognizes m6A modification in the 5'-UTR of ETV5 mRNA and recruits eukaryotic translation initiation factor 3 subunit B (eIF3B) to facilitate ETV5 translation (rather than decay), which then induces transcription of PD-L1 and VEGFA to promote HCC immune evasion and angiogenesis. RIP assay, m6A modification mapping (5'-UTR), co-IP for eIF3B recruitment, ETV5 ChIP, KD/OE experiments in vitro and in vivo Advanced science Medium 38247171
2023 YTHDF2 directly binds RIG-I (DDX58) mRNA at its coding sequence and mediates its degradation in an m6A-dependent manner in bladder cancer, suppressing RIG-I-mediated innate immune signaling and promoting immune evasion. Integrative RNA-seq and m6A-seq, RIP assay, mRNA stability assay, epistasis rescue, orthotopic mouse model Cancer research Medium 36939388
2023 YTHDF2 promotes pre-miR-126 maturation by recognizing m6A modifications in pre-miR-126 and recruiting AGO2, facilitating processing of pre-miR-126 into mature miR-126 to promote AML progression. RIP assay (YTHDF2-pre-miR-126 binding), AGO2 co-IP, forced expression of miR-126 rescue, KD/OE in AML cells and mouse models Genes & diseases Medium 37588203
2023 YTHDF2 binds m6A sites on DAPK3 mRNA 3'-UTR and facilitates its degradation in gallbladder cancer; DAPK3 inhibition rescues tumor-suppressive phenotypes from YTHDF2 deficiency and drives gemcitabine resistance. RIP-seq, MeRIP-seq, RNA-seq integration, mRNA stability assay, epistasis rescue, in vivo xenograft Cancer science Medium 37700438
2023 KRT17 causes YTHDF2 degradation through the ubiquitin-proteasome system; YTHDF2 targets CXCL10 mRNA (identified by RIP sequencing) for m6A-dependent decay, thus suppressing CXCL10-mediated T-lymphocyte recruitment in colorectal cancer. Mass spectrometry, co-IP, ubiquitin-proteasome inhibition, high-throughput RIP sequencing, YTHDF2 KD rescue Cancer immunology research Medium 37129929
2023 Ythdf2 promotes degradation of Hmox1 mRNA in an m6A-dependent manner in alveolar macrophages; myeloid-specific Ythdf2 KO mice are protected from pulmonary hypertension with elevated Hmox1, and Hmox1 inhibition reverses this protection. Myeloid-specific KO mice, mRNA stability assay, Hmox1 inhibitor epistasis, in vivo PH model Redox biology High 36801705
2023 YTHDF2 promotes aggresome formation in an m6A-independent manner by interacting with UPF1 within a misfolded polypeptide-associated complex (containing UPF1, CTIF, eEF1A1, and DCTN1); YTHDF2 increases dynein motor protein interaction with this complex, facilitating movement of misfolded polypeptides toward aggresomes. YTHDF2 KD in HeLa cells, co-IP of protein complex, dynein interaction assay, aggresome circularity/movement analysis Nature communications High 37803021
2023 YTHDF2 directly binds RXRα mRNA via RIP-qPCR and promotes its degradation, reducing RXRα expression in myeloid cells; Ythdf2 conditional KO mice show elevated MDSCs with enhanced suppressive function in autoimmune hepatitis. m6A RIP, RIP-qPCR, conditional KO mice, flow cytometry, multi-omic m6A-seq + mRNA-seq Journal of autoimmunity Medium 36642058
2023 YTHDF2 mediates decay of Ythdf2 mRNA itself (autoregulation) in an m6A-dependent manner in CD8 T cells; additionally, YTHDF2 translocates to the nucleus where it facilitates nascent RNA synthesis and interacts with IKZF1/3 to sustain transcription of their target genes, reinforcing T cell polyfunctionality. Conditional KO in T cells, m6A recognition mutant analysis, nuclear localization imaging, co-IP (YTHDF2-IKZF1/3), chromatin assays, in vivo tumor models Nature communications High 39500904
2023 Ythdf2 directly regulates mRNA stability of eukaryotic elongation factor 2 (eEF2) in cardiomyocytes (identified by cell-type specific Ribo-seq); cardiomyocyte-specific Ythdf2 deletion leads to cardiac hypertrophy, reduced function, and increased fibrosis during pressure overload and aging. Cardiomyocyte-specific Ythdf2 KO mice, Ribo-seq, mRNA stability analysis, cardiac phenotyping Journal of molecular and cellular cardiology Medium 37315764
2023 YTHDF2 binds m6A-modified Myzap mRNA and controls its stability; cardiomyocyte-specific YTHDF2 KO leads to cardiac dysfunction and upregulation of MYZAP protein, demonstrating YTHDF2 maintains cardiac homeostasis by suppressing this hypertrophic protein. Cardiomyocyte-specific KO mice, proteomics, RIP assay for YTHDF2-Myzap mRNA binding, mRNA stability assay JACC. Basic to translational science Medium 37791304
2023 YTHDF2-mediated m6A-dependent mRNA decay of Pyk2 in macrophages attenuates LPS-induced proinflammatory signaling (MAPKs, AKT) and ROS generation; Mettl3 depletion stabilizes Pyk2 mRNA via Ythdf2, and RIP-PCR confirmed direct YTHDF2-Pyk2 mRNA binding. RNA-seq, m6A mapping, RIP-PCR, Mettl3/Ythdf2 KD, Pyk2 inhibitor rescue Immunology letters Medium 37952687
2024 YTHDF2 functions as a dual m6A/m5C reader: it stabilizes m5C-modified mRNAs by recruiting PABPC1, enhancing their translation and ATP synthesis (pro-tumorigenic), while simultaneously destabilizing other m6A-modified mRNAs to promote immune evasion in B cell malignancies; YTHDF2 overexpression alone is sufficient to cause B cell transformation. m5C/m6A reader assay, co-IP (YTHDF2-PABPC1), mRNA stability and translation assay, YTHDF2 OE-driven transformation model, small-molecule inhibitor Cell High 39694037
2024 FMDV structural protein VP1 promotes autophagy (AKT-MTOR-dependent) and degrades YTHDF2 through the autophagy pathway, leading to increased GTPBP4 mRNA/protein levels; elevated GTPBP4 inhibits IRF3 binding to the Ifnb promoter, suppressing type I interferon production. Co-IP (VP1-YTHDF2 interaction), autophagy inhibitor/activator treatment, IRF3 ChIP assay, YTHDF2 KD rescue of IFN-β, in vivo GTPBP4-deficient mice Autophagy Medium 38516932
2024 IFN-γ induces autophagic degradation of tumoral YTHDF2, sensitizing tumor cells to CD8+ T cell-mediated cytotoxicity; tumoral YTHDF2 deficiency promotes CX3CL1-mediated macrophage recruitment and enhances mitochondrial respiration of CD8+ T cells by impairing tumor glycolysis. Conditional KO tumor models, CX3CL1 mRNA stabilization assay, autophagy inhibitor experiments, metabolic assays in CD8+ T cells Science immunology Medium 38820140
2024 Protein lactylation elevates YTHDF2 expression in cardiomyocytes; the intrinsic disorder region (not the m6A-binding domain) of YTHDF2 is required for its regulation of cardiomyocyte size and apoptosis via upregulating G3BP1; exercise-induced downregulation of YTHDF2 is required for physiological cardiac hypertrophy. Lactylation inhibition, YTHDF2 domain deletion mutant analysis, OGD/R model, YTHDF2 KD/OE in cardiomyocytes, in vivo ischemia/reperfusion model Basic research in cardiology Medium 38563985
2024 YTHDF2 stabilizes Cx3cl1 transcripts in an m6A-dependent manner in hepatocytes (identified by liver-specific KO model), regulating CD8+ T cell recruitment and antitumor immunity; OXA upregulates YTHDF2 expression via the cGAS-STING signaling pathway. Liver-specific Ythdf2 KO mice, mRNA stability assay for Cx3cl1, cGAS-STING pathway analysis, tumor-bearing liver models Molecular cancer Medium 39237909
2024 YTHDF2 controls mRNA stability of the ubiquitin ligase ASB2; in skeletal muscle, ASB2 upregulation upon YTHDF2 loss activates SMAD3-dependent anti-growth gene programs, thereby impairing postnatal muscle growth and hypertrophic response. Muscle-specific Ythdf2 KO mice, mRNA stability assay for ASB2, SMAD3 pathway analysis, hypertrophic stimuli experiments Nature communications High 38467649
2024 OTUB1 (deubiquitinase) increases YTHDF2 protein stability by blocking ubiquitin transfer to YTHDF2 independently of its deubiquitinase activity; stabilized YTHDF2 promotes m6A-dependent PRSS8 mRNA degradation, reducing PRSS8-mediated nuclear β-catenin suppression via E-cadherin in prostate cancer. In vivo and in vitro ubiquitination assays, co-IP (OTUB1-YTHDF2), YTHDF2 RIP assay for PRSS8 mRNA, mRNA stability assay, cellular/mouse models The Journal of biological chemistry High 38462165
2024 Ythdf2 in pulmonary artery smooth muscle cells stabilizes (rather than degrades) Myadm mRNA in an m6A-dependent manner; this paradoxical stabilization promotes PASMC proliferation and pulmonary hypertension via an m6A/Myadm/p21 pathway. Smooth muscle cell-specific Ythdf2 KO mice, proteomics, m6A sequencing, RIP assay, Myadm siRNA rescue, in vivo PH model Hypertension Medium 38832511
2024 ROS activates YTHDF2 and promotes degradation of m6A-modified FOXO3 mRNA; loss of FOXO3 impairs its ability to recruit CBP and Med1 to activate TIMP1 expression, increasing MMP activity and contributing to intervertebral disc degeneration. Pharmacological YTHDF2 inhibition restores FOXO3/TIMP1/MMP balance. iTRAQ proteomics, YTHDF2 KD/OE, m6A-modified FOXO3 mRNA stability assay, FOXO3-ChIP (CBP/Med1 recruitment), YTHDF2 inhibitor DC-Y13-27 in vivo Cellular and molecular life sciences Medium 39625652
2024 lncRNA JPX directly interacts with YTHDF2 and blocks USP10-mediated deubiquitination/protection of YTHDF2, promoting YTHDF2 ubiquitin-dependent degradation; reduced YTHDF2 stabilizes BMP2 mRNA and activates AKT phosphorylation in melanoma. RNA pull-down, RIP, co-IP, Western blot, RNA-seq, ubiquitination assay Molecular cancer research Medium 38441563
2024 Conditional deletion of Ythdf2 from proliferating hippocampal NSCs elevates quiescence acquisition; Ythdf2 targets multiple TGF-β signaling pathway components (ligands, receptors, transcription regulators) for m6A-dependent mRNA decay, and TGF-β signaling suppression rescues elevated quiescence in Ythdf2-deficient NSCs. Conditional KO in NSCs, multimodal m6A/YTHDF2 binding/mRNA decay profiling, TGF-β inhibitor rescue, in vivo/in vitro assays Cell stem cell High 39476834
2024 Ythdf2 directly regulates the mRNA stability of Ace and Bmp4 as an m6A reader in retinal microglia; Ythdf2 loss increases Ace and Bmp4 expression, causing aberrant microglial activation and pathological angiogenesis; pharmacological inhibition of Ace or Bmp4 alleviates the Ythdf2-deficiency-driven microvascular disease. Microglia-specific Ythdf2 KO mice, scRNA-seq, mRNA stability assay, captopril/noggin pharmacological rescue, in vivo OIR model Journal of advanced research Medium 41627954
2025 YTHDF2 forms a complex with eIF3F and DDX1 to enhance translation of m6A-modified mRNAs encoding microtubule-associated proteins in ovarian cancer, thereby promoting cancer progression and paclitaxel resistance independently of its mRNA decay function; a small-molecule inhibitor targeting YTHDF2 reverses this translational enhancement. Co-IP (YTHDF2-eIF3F-DDX1), mRNA stability vs. translation assay, virtual screening for inhibitor, eCLIP, functional paclitaxel resistance assay Molecular cell High 40480228
2025 YTHDF2 ablation in naive CD4+ T cells promotes Th9 differentiation by stabilizing Gata3 and Smad3 mRNAs under IL-4 and TGF-β signaling respectively; Ythdf2-deficient Th9 cells produce more IL-9 and IL-21, enhancing CD8+ T cell and NK cell tumor infiltration and cytotoxicity. Ythdf2 KO in mouse and human naive CD4+ T cells, mRNA stability assay for Gata3/Smad3, in vivo antitumor models, CAR-Th9 experiments Nature immunology High 40826275
2025 Phenylpyrazole compounds (e.g., CK-75) bind a small hydrophobic pocket on the YTH domain of YTHDF2, inhibiting its m6A-binding activity; eCLIP confirmed altered global RNA-binding patterns of YTHDF2 upon CK-75 treatment, and the compounds induce cell cycle arrest and apoptosis in cancer cells. Small-molecule binding to YTH domain (structural pocket), eCLIP, cell viability/apoptosis assays JACS Au Medium 40017738

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Histone lactylation drives oncogenesis by facilitating m6A reader protein YTHDF2 expression in ocular melanoma. Genome biology 776 33726814
2019 Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. Cell stem cell 409 31031138
2018 YTHDF2 suppresses cell proliferation and growth via destabilizing the EGFR mRNA in hepatocellular carcinoma. Cancer letters 297 30423408
2019 YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma. Molecular cancer 289 31735169
2021 EGFR/SRC/ERK-stabilized YTHDF2 promotes cholesterol dysregulation and invasive growth of glioblastoma. Nature communications 254 33420027
2018 Ythdf2-mediated m6A mRNA clearance modulates neural development in mice. Genome biology 249 29855337
2021 Hypoxia inducible lncRNA-CBSLR modulates ferroptosis through m6A-YTHDF2-dependent modulation of CBS in gastric cancer. Journal of advanced research 222 35499052
2019 m6A Reader YTHDF2 Regulates LPS-Induced Inflammatory Response. International journal of molecular sciences 195 30875984
2023 YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8+ T cells. Nature immunology 186 36658237
2023 YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. Cancer cell 185 37236197
2021 The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity. The Journal of experimental medicine 171 34160549
2021 Inhibition of YTHDF2 triggers proteotoxic cell death in MYC-driven breast cancer. Molecular cell 151 34216543
2023 O-GlcNAcylation of YTHDF2 promotes HBV-related hepatocellular carcinoma progression in an N6-methyladenosine-dependent manner. Signal transduction and targeted therapy 138 36765030
2021 The mRNA m6A reader YTHDF2 suppresses proinflammatory pathways and sustains hematopoietic stem cell function. The Journal of experimental medicine 118 33156926
2021 The biological function of m6A reader YTHDF2 and its role in human disease. Cancer cell international 111 33593354
2019 YTHDF2 Binds to 5-Methylcytosine in RNA and Modulates the Maturation of Ribosomal RNA. Analytical chemistry 99 31815440
2021 RNA m6A reader YTHDF2 facilitates lung adenocarcinoma cell proliferation and metastasis by targeting the AXIN1/Wnt/β-catenin signaling. Cell death & disease 92 33980824
2023 The m6A Reader YTHDF2 Promotes Bladder Cancer Progression by Suppressing RIG-I-Mediated Immune Response. Cancer research 86 36939388
2022 m6A binding protein YTHDF2 in cancer. Experimental hematology & oncology 82 35382893
2021 METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5. Molecular oncology 75 33411363
2020 YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells. Journal of ovarian research 73 32948220
2021 FTO promotes multiple myeloma progression by posttranscriptional activation of HSF1 in an m6A-YTHDF2-dependent manner. Molecular therapy : the journal of the American Society of Gene Therapy 72 34915192
2020 YTHDF2/3 Are Required for Somatic Reprogramming through Different RNA Deadenylation Pathways. Cell reports 68 32905781
2023 ALKBH5/YTHDF2-mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation. Clinical and translational medicine 65 37381158
2024 Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner. Redox biology 64 38184996
2024 YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD-L1/VEGFA Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 64 38247171
2023 KRT17 Promotes T-lymphocyte Infiltration Through the YTHDF2-CXCL10 Axis in Colorectal Cancer. Cancer immunology research 63 37129929
2020 YTHDF2 promotes mitotic entry and is regulated by cell cycle mediators. PLoS biology 63 32267835
2022 Gene amplification-driven RNA methyltransferase KIAA1429 promotes tumorigenesis by regulating BTG2 via m6A-YTHDF2-dependent in lung adenocarcinoma. Cancer communications (London, England) 62 35730068
2022 YTHDF2 promotes intrahepatic cholangiocarcinoma progression and desensitises cisplatin treatment by increasing CDKN1B mRNA degradation. Clinical and translational medicine 60 35696608
2023 HSP90β Impedes STUB1-Induced Ubiquitination of YTHDF2 to Drive Sorafenib Resistance in Hepatocellular Carcinoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 58 37515378
2020 YTHDF2 promotes spermagonial adhesion through modulating MMPs decay via m6A/mRNA pathway. Cell death & disease 58 31959747
2024 Exercise training decreases lactylation and prevents myocardial ischemia-reperfusion injury by inhibiting YTHDF2. Basic research in cardiology 55 38563985
2023 YTHDF2/m6 A/NF-κB axis controls anti-tumor immunity by regulating intratumoral Tregs. The EMBO journal 53 37345898
2024 The tumor-intrinsic role of the m6A reader YTHDF2 in regulating immune evasion. Science immunology 52 38820140
2021 YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway. Frontiers in genetics 52 33505426
2024 YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies. Cell 51 39694037
2020 FTO regulates ocular angiogenesis via m6A-YTHDF2-dependent mechanism. Experimental eye research 50 32531187
2023 Ythdf2 promotes pulmonary hypertension by suppressing Hmox1-dependent anti-inflammatory and antioxidant function in alveolar macrophages. Redox biology 47 36801705
2021 N-methyladenosine reader YTHDF2-mediated long noncoding RNA FENDRR degradation promotes cell proliferation in endometrioid endometrial carcinoma. Laboratory investigation; a journal of technical methods and pathology 46 33692441
2021 YTHDF2 mediates LPS-induced osteoclastogenesis and inflammatory response via the NF-κB and MAPK signaling pathways. Cellular signalling 42 34089814
2022 YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation. Cell reports 41 35508130
2021 m6 A reader protein YTHDF2 regulates spermatogenesis by timely clearance of phase-specific transcripts. Cell proliferation 39 34850470
2022 YTHDF2 promotes multiple myeloma cell proliferation via STAT5A/MAP2K2/p-ERK axis. Oncogene 37 35075244
2024 Foot-and-mouth disease virus VP1 degrades YTHDF2 through autophagy to regulate IRF3 activity for viral replication. Autophagy 35 38516932
2024 PRMT6-mediated transcriptional activation of ythdf2 promotes glioblastoma migration, invasion, and emt via the wnt-β-catenin pathway. Journal of experimental & clinical cancer research : CR 35 38637831
2023 RNA m6A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression. Genes & diseases 33 37588203
2023 FTO-Nrf2 axis regulates bisphenol F-induced leydig cell toxicity in an m6A-YTHDF2-dependent manner. Environmental pollution (Barking, Essex : 1987) 32 36878272
2023 Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism. Journal of advanced research 32 37865189
2022 YTHDF2 interference suppresses the EMT of cervical cancer cells and enhances cisplatin chemosensitivity by regulating AXIN1. Drug development research 32 35489084
2022 DDX5/METTL3-METTL14/YTHDF2 Axis Regulates Replication of Influenza A Virus. Microbiology spectrum 30 35583334
2020 YTHDF2 Regulates Maternal Transcriptome Degradation and Embryo Development in Goat. Frontiers in cell and developmental biology 30 33117808
2020 Melatonin antagonizes ovarian aging via YTHDF2-MAPK-NF-κB pathway. Genes & diseases 30 35224163
2022 YTHDF2 Regulates Macrophage Polarization through NF-κB and MAPK Signaling Pathway Inhibition or p53 Degradation. Disease markers 29 36277978
2024 YTHDF2 in peritumoral hepatocytes mediates chemotherapy-induced antitumor immune responses through CX3CL1-mediated CD8+ T cell recruitment. Molecular cancer 28 39237909
2023 YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths. National science review 28 38152479
2022 The lncRNA MIAT regulates CPT-1a mediated cardiac hypertrophy through m6A RNA methylation reading protein Ythdf2. Cell death discovery 26 35383152
2023 Suppression of YTHDF2 attenuates autoimmune hepatitis by expansion of myeloid-derived suppressor cells. Journal of autoimmunity 25 36642058
2023 Epitranscriptional regulation of TGF-β pseudoreceptor BAMBI by m6A/YTHDF2 drives extrinsic radioresistance. The Journal of clinical investigation 25 38099498
2024 YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity. Nature communications 24 39500904
2023 YTHDF2 exerts tumor-suppressor roles in gastric cancer via up-regulating PPP2CA independently of m6A modification. Biological procedures online 23 36870954
2023 N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21cip1/waf1/CDK2-Cyclin E1 axis-mediated cell cycle transition. Oncogene 23 37012388
2020 YTHDF2 correlates with tumor immune infiltrates in lower-grade glioma. Aging 23 32986017
2022 Metformin combats obesity by targeting FTO in an m6A-YTHDF2-dependent manner. Journal of drug targeting 22 35481401
2024 KIAA1429 promotes gastric cancer progression by destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. Journal of translational medicine 21 38902717
2023 RNA methylation reading protein YTHDF2 relieves myocardial ischemia-reperfusion injury by downregulating BNIP3 via m6A modification. Human cell 21 37500815
2023 Mettl3/Ythdf2 regulate macrophage inflammation and ROS generation by controlling Pyk2 mRNA stability. Immunology letters 20 37952687
2025 YTHDF2-mediated m6A modification of ONECUT2 promotes stemness and oxaliplatin resistance in gastric cancer through transcriptionally activating TFPI. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 19 39823826
2025 YTHDF2: a key RNA reader and antitumor target. Trends in immunology 19 40399203
2022 Expression and clinical significance of the m6A reader YTHDF2 in peripheral blood mononuclear cells from rheumatoid arthritis patients. Journal of immunotoxicology 19 35776431
2023 Ythdf2 regulates cardiac remodeling through its mRNA target transcripts. Journal of molecular and cellular cardiology 18 37315764
2022 YTHDF2 Inhibits the Migration and Invasion of Lung Adenocarcinoma by Negatively Regulating the FAM83D-TGFβ1-SMAD2/3 Pathway. Frontiers in oncology 18 35186724
2023 YBX2 modulates mRNA stability via interaction with YTHDF2 in endometrial cancer cells. Experimental cell research 17 37030331
2023 Loss of YTHDF2 Alters the Expression of m6A-Modified Myzap and Causes Adverse Cardiac Remodeling. JACC. Basic to translational science 17 37791304
2021 PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation. Cells 17 34200988
2025 Phenylpyrazoles as Inhibitors of the m6A RNA-Binding Protein YTHDF2. JACS Au 16 40017738
2024 FTO mediates bisphenol F-induced blood-testis barrier impairment through regulating ferroptosis via YTHDF1/TfRc and YTHDF2/SLC7A11 signal axis. Environmental pollution (Barking, Essex : 1987) 16 38996995
2024 m6A/YTHDF2-mediated mRNA decay targets TGF-β signaling to suppress the quiescence acquisition of early postnatal mouse hippocampal NSCs. Cell stem cell 16 39476834
2023 YTHDF2 promotes gallbladder cancer progression and gemcitabine resistance via m6A-dependent DAPK3 degradation. Cancer science 16 37700438
2025 The RNA-stability-independent role of the RNA m6A reader YTHDF2 in promoting protein translation to confer tumor chemotherapy resistance. Molecular cell 15 40480228
2025 Ythdf2 loss in microglia aggravates ischemic retinopathy by increasing microglia activation and microvascular anomalies. Journal of advanced research 15 41627954
2024 Nicotine-derived NNK promotes CRC progression through activating TMUB1/AKT pathway in METTL14/YTHDF2-mediated m6A manner. Journal of hazardous materials 15 38341886
2024 lncRNA JPX Promotes Tumor Progression by Interacting with and Destabilizing YTHDF2 in Cutaneous Melanoma. Molecular cancer research : MCR 15 38441563
2022 Expression and Clinical Significance of the m6A RNA-Binding Proteins YTHDF2 in Peripheral Blood Mononuclear Cells From New-Onset Ankylosing Spondylitis. Frontiers in medicine 14 35755020
2021 YTHDF2 Suppresses Notch Signaling through Post-transcriptional Regulation on Notch1. International journal of biological sciences 14 34671198
2024 BCLAF1 drives esophageal squamous cell carcinoma progression through regulation of YTHDF2-dependent SIX1 mRNA degradation. Cancer letters 12 38636894
2024 METTL3 regulates cartilage development and homeostasis by affecting Lats1 mRNA stability in an m6A-YTHDF2-dependent manner. Cell reports 12 39088322
2024 Biological functions of the m6A reader YTHDF2 and its role in central nervous system disorders. Biochemical pharmacology 12 39424201
2024 YTHDF2-dependent m6A modification of FOXO3 mRNA mediates TIMP1 expression and contributes to intervertebral disc degeneration following ROS stimulation. Cellular and molecular life sciences : CMLS 12 39625652
2022 N6-Methyladenosine Reader YTHDF2 Enhances Non-Small-Cell Lung Cancer Cell Proliferation and Metastasis through Mediating circ_SFMBT2 Degradation. Contrast media & molecular imaging 12 35924072
2025 Histone lactylation-driven YTHDF2 promotes non-small cell lung cancer cell glycolysis and stemness by recognizing m6A modification of SFRP2. Biochemical pharmacology 11 40619016
2025 Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy. Nature immunology 11 40826275
2024 YTHDF2 governs muscle size through a targeted modulation of proteostasis. Nature communications 11 38467649
2024 Smooth Muscle Ythdf2 Abrogation Ameliorates Pulmonary Vascular Remodeling by Regulating Myadm Transcript Stability. Hypertension (Dallas, Tex. : 1979) 11 38832511
2023 YTHDF2 Regulates Cell Growth and Cycle by Facilitating KDM1A mRNA Stability. The American journal of pathology 11 36681189
2023 METTL3/YTHDF2 m6A axis promotes the malignant progression of bladder cancer by epigenetically suppressing RRAS. Oncology reports 11 36960869
2023 YTHDF2 facilitates aggresome formation via UPF1 in an m6A-independent manner. Nature communications 11 37803021
2023 Ythdf2-mediated STK11 mRNA decay supports myogenesis by inhibiting the AMPK/mTOR pathway. International journal of biological macromolecules 11 37884231
2022 Novel insights into roles of N6-methyladenosine reader YTHDF2 in cancer progression. Journal of cancer research and clinical oncology 11 35763107
2024 YTHDF2 protein stabilization by the deubiquitinase OTUB1 promotes prostate cancer cell proliferation via PRSS8 mRNA degradation. The Journal of biological chemistry 9 38462165

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