Affinage

ALKBH5

RNA demethylase ALKBH5 · UniProt Q6P6C2

Length
394 aa
Mass
44.3 kDa
Annotated
2026-06-09
100 papers in source corpus 51 papers cited in narrative 53 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

ALKBH5 is a mammalian RNA demethylase that oxidatively reverses N6-methyladenosine (m6A) in mRNA in vitro and in vivo, the second identified mammalian m6A eraser, controlling mRNA export, nuclear speckle assembly, and RNA metabolism (PMID:23177736). Crystal structures of ALKBH5 bound to m6A-containing single-stranded RNA show the substrate engaged in a 5'-3' orientation, define an (A/G)m6AC consensus preference, and identify a Lys132/Tyr139 proton-shuttle network that drives hemiaminal-intermediate demethylation and formaldehyde release (PMID:35333330). Substrate selection is not intrinsic to the enzyme alone: the RNA-binding co-factor RBM33 forms a complex with ALKBH5, removes its inhibitory SUMOylation, and recruits it to specific transcripts such as DDIT4 (PMID:37257451). ALKBH5 activity and localization are tuned by a layered post-translational code—ROS/ERK-JNK-driven SUMOylation that blocks substrate access (PMID:34048572), kinase phosphorylation (SRC, LATS2, MST4, PKA) that controls nuclear retention, export, or stability (PMID:37979586, PMID:38568805, PMID:39990235, PMID:40014709), PRMT5-catalyzed arginine methylation that promotes TRIM28-dependent degradation (PMID:39781264), lactylation that licenses IFN-β mRNA demethylation (PMID:39413129), and deubiquitination by USP9X, USP36, and USP14 that stabilizes the protein (PMID:36239338, PMID:37454738, PMID:39990235). Through demethylation of defined mRNA targets, ALKBH5 alters transcript stability or translation—generally protecting transcripts from m6A-reader-mediated decay (e.g. YTHDF2) or shifting reader engagement (IGF2BP, YTHDF1)—to regulate processes including spermatogenesis (PMID:23177736), oocyte maternal-RNA clearance via IGF2BP2 (PMID:37848452), blood-testis barrier integrity through Cdh2 (PMID:36418936), hematopoietic stem cell metabolism via OGDH (PMID:37742191), neutrophil mobilization and migration (PMID:38114747, PMID:35764614), astrocytic glutamate homeostasis via GLT-1 (PMID:38773146), and hepatic glucose/lipid metabolism (PMID:40014709). ALKBH5 also acts on non-coding RNA: under hypoxia it condenses into paraspeckles through its C-terminal disordered region and demethylates NEAT1 to drive paraspeckle assembly and CXCL8-mediated macrophage recruitment (PMID:34670781, PMID:37474102). Dysregulated ALKBH5 drives tumorigenesis in glioblastoma, AML, multiple myeloma, colorectal, gastric, and other cancers through context-dependent stabilization or destabilization of oncogenic transcripts including FOXM1, TACC3, and AXL (PMID:28344040, PMID:32402250, PMID:37169182).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2012 High

    Established that mammals possess a second, dedicated m6A eraser, defining ALKBH5 as an RNA demethylase with a physiological role in fertility.

    Evidence In vitro demethylation assay plus Alkbh5-knockout mice with mRNA export and nuclear speckle readouts and testis transcriptomics

    PMID:23177736

    Open questions at the time
    • No structural basis for substrate recognition
    • Direct mRNA targets in spermatocytes not individually defined
  2. 2022 High

    Resolved how ALKBH5 recognizes and chemically processes its substrate, explaining sequence preference and the catalytic chemistry distinguishing it from DNA-acting AlkB members.

    Evidence Three X-ray crystal structures with m6A ssRNA, biochemical demethylation assays, and active-site mutagenesis

    PMID:35333330

    Open questions at the time
    • Structures do not address how cellular co-factors redirect substrate choice
    • No structure of post-translationally modified ALKBH5
  3. 2017 High

    Showed that ALKBH5 acts on specific nascent transcripts in disease, demethylating FOXM1 to stabilize it and sustain glioblastoma stem cell proliferation, guided by an antisense lncRNA.

    Evidence m6A-seq, reciprocal RIP, ALKBH5 knockdown in patient-derived GSCs, and in vivo tumor models

    PMID:28344040

    Open questions at the time
    • Mechanism by which FOXM1-AS tethers ALKBH5 to nascent RNA not structurally defined
    • Generalizability of antisense-RNA targeting to other transcripts unknown
  4. 2020 High

    Demonstrated ALKBH5 as a selective dependency of leukemia stem cells (dispensable for normal hematopoiesis) acting through TACC3 and AXL, and showed its expression is set epigenetically via KDM4C/H3K9me3.

    Evidence Conditional KO mice, human AML lines, m6A-seq/RNA-seq, ChIP-seq/ATAC-seq, and in vivo leukemia models

    PMID:32402250 PMID:32402251

    Open questions at the time
    • Why LSCs but not normal HSCs depend on ALKBH5 not fully explained
    • Reader proteins decoding the retained m6A marks not defined in these studies
  5. 2021 High

    Revealed that ALKBH5 enzymatic activity is gated by SUMOylation downstream of ROS/ERK-JNK signaling, providing a signal-responsive switch over global m6A.

    Evidence SUMOylation assays, ERK/JNK inhibition, ROS induction in cells and mouse HSPCs, and SUMO-site mutagenesis

    PMID:34048572

    Open questions at the time
    • SUMO ligase responsible not identified
    • How SUMOylation physically blocks substrate access not structurally resolved
  6. 2021 Medium

    Extended the demethylation-stabilization logic across diverse cancers and tissues, showing ALKBH5 acts on target-specific transcripts (TRAF1, FOXM1, USP1, NANOG, IGF1R) to drive distinct oncogenic programs.

    Evidence MeRIP-qPCR, mRNA stability assays, knockdown/rescue, and in vivo tumor models across myeloma, melanoma, T-ALL, ovarian, and endometrial cancers

    PMID:32329191 PMID:32913456 PMID:33428593 PMID:34169564 PMID:34759347

    Open questions at the time
    • Several rely on single-lab MeRIP without reciprocal validation
    • Direct ALKBH5-transcript binding not always demonstrated
  7. 2022 Medium

    Showed ALKBH5 also regulates non-coding RNA and organizes membraneless compartments, condensing via its disordered C-terminus into paraspeckles to demethylate and stabilize NEAT1 under hypoxia.

    Evidence m6A-seq, NEAT1 stability and SFPQ ChIP assays, phase-separation assays, and cIDR deletion mutants

    PMID:34670781 PMID:37474102

    Open questions at the time
    • Whether condensation is required for catalysis on mRNA targets is unresolved
    • Triggers of hypoxia-induced condensation not fully mapped
  8. 2022 High

    Established ALKBH5 as a tissue-level regulator through cell-type-specific knockouts, governing blood-testis barrier integrity, hematopoietic metabolism, oocyte RNA clearance, neutrophil function, and γδ T cell development via discrete mRNA targets.

    Evidence Cell-type-specific Alkbh5 KO mice, m6A-seq, polysome fractionation, metabolomics, and in vivo infection/transplantation models

    PMID:35764614 PMID:35939687 PMID:36418936 PMID:37742191 PMID:37848452 PMID:38114747

    Open questions at the time
    • Reader partners (IGF2BP1/2/3, YTHDF1/2) coupling differs by target and is incompletely mapped
    • Whether single targets account for full phenotypes is uncertain
  9. 2023 High

    Identified RBM33 as the substrate-recruiting co-factor that both de-SUMOylates and activates ALKBH5, solving how the enzyme achieves transcript selectivity.

    Evidence Reciprocal Co-IP, in vitro demethylase assays, SUMOylation assays, and m6A-seq in HNSCC targeting DDIT4

    PMID:37257451

    Open questions at the time
    • Whether RBM33 directs ALKBH5 to its many other reported targets is untested
    • Other adaptor co-factors not excluded
  10. 2023 High

    Defined an extensive deubiquitinase/kinase network (USP9X, USP36, USP14, SRC, LATS2, MST4) controlling ALKBH5 protein abundance and nuclear retention, frequently within positive feedback loops sustaining glioblastoma and AML stem cells.

    Evidence Mass spectrometry, Co-IP, site-specific ubiquitination and phospho-mutagenesis, m6A-seq, and xenograft models

    PMID:36239338 PMID:37454738 PMID:37979586 PMID:38568805 PMID:39990235

    Open questions at the time
    • The E3 ligases opposing these DUBs are largely undefined
    • How multiple PTMs are integrated on the same molecule is unknown
  11. 2024 Medium

    Expanded the PTM repertoire to lactylation (ESCO2/SIRT6) and arginine methylation (PRMT5/TRIM28), linking ALKBH5 regulation to antiviral innate immunity and to degradation-driven cancer immune evasion.

    Evidence Lactylation/methylation mass spectrometry, writer-eraser Co-IP, in vitro PRMT5 methylation and TRIM28 ubiquitination assays, RIP, and functional immune/tumor assays

    PMID:39413129 PMID:39781264

    Open questions at the time
    • Crosstalk between lactylation, SUMOylation, and methylation on the same residues unresolved
    • PRMT5/TRIM28 axis shown in single lab
  12. 2025 High

    Connected ALKBH5 regulation to systemic physiology and therapy resistance, showing PKA-driven phosphorylation/relocalization governs hepatic glucose-lipid metabolism and ferroptosis, and KRAS-ERK/JNK SUMOylation confers platinum resistance via DNA-repair transcripts.

    Evidence PKA phosphorylation assays, hepatocyte-specific KO, SUMO-deficient mutants, NER and ferroptosis assays, and diabetic/NSCLC in vivo models

    PMID:39901038 PMID:39960727 PMID:40014709

    Open questions at the time
    • Phospho-sites for the PKA-ferroptosis axis not all mapped
    • Whether hepatic and tumor PKA effects share the same mechanism is unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the combinatorial post-translational code, co-factor recruitment, and phase separation are integrated to select among the many reported ALKBH5 targets in a given cell remains unresolved.
  • No unified model linking PTM state to target choice
  • Reader-protein coupling that dictates stabilization vs destabilization not systematically defined
  • E3 ligases and SUMO ligases acting on ALKBH5 largely unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 5 GO:0003723 RNA binding 4 GO:0016491 oxidoreductase activity 2 GO:0016787 hydrolase activity 1
Localization
GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-8953854 Metabolism of RNA 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4
Partners
LATS2MST4PRMT5RBM33SRCUSP14USP36USP9X
Complex memberships
paraspeckle

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 ALKBH5 is a mammalian RNA demethylase that oxidatively reverses N6-methyladenosine (m6A) in mRNA in vitro and in vivo. Its demethylation activity affects mRNA export and RNA metabolism, as well as assembly of mRNA processing factors in nuclear speckles. Alkbh5-deficient male mice show increased m6A in mRNA and impaired fertility due to apoptosis of meiotic metaphase-stage spermatocytes. In vitro demethylation assay, Alkbh5-knockout mice, mRNA export and nuclear speckle assembly assays, transcriptome profiling of testes Molecular cell High 23177736
2022 Crystal structures of ALKBH5 in complex with m6A-containing single-stranded RNA 8-mer revealed that the RNA substrate binds in a 5'-3' orientation opposite to that of DNA substrates in other AlkB members. The structures defined the (A/G)m6AC consensus sequence preference and a proton shuttle network involving Lys132 and Tyr139 that enables efficient hemiaminal intermediate demethylation to produce formaldehyde. X-ray crystallography (three crystal structures), biochemical demethylation assays, mutagenesis of active-site residues Nucleic acids research High 35333330
2017 ALKBH5 demethylates FOXM1 nascent transcripts in glioblastoma stem-like cells (GSCs), leading to enhanced FOXM1 mRNA stability and expression. A long non-coding RNA antisense to FOXM1 (FOXM1-AS) promotes the interaction of ALKBH5 with FOXM1 nascent transcripts. ALKBH5 silencing suppresses GSC proliferation and tumorigenesis through this FOXM1 axis. Integrated transcriptome and m6A-seq, RNA immunoprecipitation, ALKBH5 knockdown in patient-derived GSCs, in vivo tumor models Cancer cell High 28344040
2021 ROS induces ALKBH5 SUMOylation via ERK/JNK signaling, which inhibits ALKBH5 m6A demethylase activity by blocking substrate accessibility, thereby globally increasing mRNA m6A levels and inducing DNA damage response genes. This ERK/JNK/ALKBH5-PTMs/m6A axis is activated in hematopoietic stem/progenitor cells in vivo. SUMOylation assays, ERK/JNK inhibitor treatments, ROS induction in cell lines and mouse HSPCs, m6A quantification, mutagenesis of SUMOylation sites Nucleic acids research High 34048572
2023 RBM33 (RNA-binding motif protein 33) forms a complex with ALKBH5 and acts as a substrate-recruiting co-factor that (1) recruits ALKBH5 to specific m6A-marked mRNA targets and (2) activates ALKBH5 demethylase activity by removing its SUMOylation. This interaction selectively directs ALKBH5 to demethylate DDIT4 mRNA to promote autophagy in HNSCC. Co-immunoprecipitation, in vitro demethylase activity assays, SUMOylation assays, m6A-seq, RBM33 knockdown in cancer cells Molecular cell High 37257451
2023 EGFR signaling retains ALKBH5 in the nucleus of glioblastoma stem cells by activating SRC kinase, which phosphorylates ALKBH5 and inhibits CRM1-mediated nuclear export. Nuclear ALKBH5 demethylates GCLM mRNA; reduced m6A on GCLM mRNA stabilizes it (preventing YTHDF2-mediated decay), thereby protecting against ferroptosis. EGFR/SRC inhibition, ALKBH5 phosphorylation assays, nuclear fractionation, YTHDF2-dependent GCLM mRNA decay assays, m6A-seq, GSC in vivo models Molecular cell High 37979586
2023 USP36 deubiquitinase directly binds ALKBH5, removes its polyubiquitin chain, and stabilizes the ALKBH5 protein in glioblastoma. USP36 depletion reduces ALKBH5 levels, impairs glioblastoma stem cell self-renewal, and inhibits in vivo tumor growth. Mass spectrometry, co-immunoprecipitation, in vivo and in vitro ubiquitination assays, USP36 knockdown in GSCs, intracranial tumor xenografts Neuro-oncology High 36239338
2023 USP9X deubiquitinase directly binds ALKBH5, removes K48-linked polyubiquitin at K57, and stabilizes the ALKBH5 protein in AML cells. USP9X depletion reduces ALKBH5 levels and promotes AML cell apoptosis; ectopic ALKBH5 expression partially rescues USP9X knockdown effects. Mass spectrometry, co-immunoprecipitation, K48-linked ubiquitination assays, site-specific mutagenesis (K57), genetic knockdown, murine AML model The Journal of biological chemistry High 37454738
2020 ALKBH5 is required for AML development and leukemia stem cell self-renewal but is dispensable for normal hematopoiesis. Mechanistically, ALKBH5 demethylates TACC3 mRNA, stabilizing it and promoting TACC3 protein expression, which drives leukemogenesis. Alkbh5 conditional knockout mice, human AML cell lines, m6A-seq, RNA-seq, MeRIP-qPCR, in vivo AML models Cell stem cell High 32402250
2020 KDM4C histone demethylase regulates ALKBH5 expression in AML by reducing H3K9me3 at the ALKBH5 locus, increasing chromatin accessibility, and promoting MYB/Pol II recruitment. ALKBH5 in turn affects AXL mRNA stability in an m6A-dependent manner to maintain leukemia stem cell function. ChIP-seq, ATAC-seq, chromatin accessibility assays, KDM4C knockdown, MeRIP-seq, AML mouse models Cell stem cell High 32402251
2019 METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA in cardiomyocytes. METTL3 methylates TFEB 3'-UTR at two m6A residues, promoting HNRNPD binding and decreasing TFEB expression. ALKBH5 demethylates these sites to reverse the effect. TFEB reciprocally binds the ALKBH5 promoter to induce its transcription, establishing a feedback loop. m6A-seq, RIP, ChIP, METTL3/ALKBH5 knockdown and overexpression in cardiomyocytes, promoter luciferase assay, murine I/R model Autophagy High 30870073
2024 ALKBH5 undergoes lactylation catalyzed by acetyltransferase ESCO2 (increased during viral infection) and is de-lactylated by SIRT6. Lactylated ALKBH5 binds IFN-β mRNA and demethylates its m6A modifications, promoting IFN-β mRNA biogenesis and antiviral innate immune responses against HSV-1, KSHV, and mpox virus. Lactylation mass spectrometry, ESCO2/SIRT6 co-immunoprecipitation, RIP of IFN-β mRNA, m6A quantification, viral infection assays, ESCO2 overexpression/SIRT6 depletion Proceedings of the National Academy of Sciences of the United States of America High 39413129
2025 KRAS mutants activate ERK/JNK signaling in NSCLC, which promotes ALKBH5 SUMOylation (inhibiting its demethylase activity), resulting in increased m6A methylation on DDB2 and XPC mRNAs. Stabilization of these DNA repair transcripts enhances nucleotide excision repair, conferring platinum resistance. A SUMOylation-deficient ALKBH5 mutant restores platinum sensitivity. SUMOylation assays, m6A-seq, RNA stability assays, NER functional assays, ALKBH5 mutagenesis, in vivo xenograft models with KRAS mutant NSCLC The Journal of clinical investigation High 39960727
2025 Protein kinase A (PKA) phosphorylates ALKBH5, promoting its degradation. Loss of ALKBH5 maintains m6A modification on GPX4 mRNA, stabilizing GPX4 and thereby suppressing ferroptosis. PKA thus acts as a regulator of ferroptosis through the ALKBH5-GPX4 m6A axis. PKA phosphorylation assays, ALKBH5 deletion/reconstitution, m6A quantification of GPX4 mRNA, ferroptosis assays, in vivo tumor models Cell death and differentiation Medium 39901038
2021 ALKBH5 demethylates FOXM1 mRNA in uveal melanoma, increasing its stability and expression, promoting tumor growth and metastasis via EMT. EP300-mediated H3K27 acetylation at the ALKBH5 locus activates ALKBH5 transcription. MeRIP-qPCR for m6A on FOXM1 mRNA, ALKBH5 knockdown in UM cell lines, in vivo xenograft model, ChIP for H3K27ac Aging Medium 33428593
2022 ALKBH5 mediates m6A demethylation of NEAT1 lncRNA under hypoxia, stabilizing NEAT1 and facilitating paraspeckle assembly. This causes relocalization of transcriptional repressor SFPQ from the CXCL8 promoter to paraspeckles, upregulating CXCL8/IL8 secretion and promoting tumor-associated macrophage recruitment in GBM. m6A-seq on hypoxic GBM cells, NEAT1 stability assays, SFPQ chromatin immunoprecipitation, ALKBH5 depletion/inactivation, allograft tumor models Cancer research High 34670781
2023 The disordered C-terminal intrinsically disordered region (cIDR) of ALKBH5 promotes liquid-liquid phase separation and incorporation into paraspeckles. Under hypoxia, rapid ALKBH5 condensation in paraspeckles induces m6A demethylation of NEAT1, further facilitating paraspeckle assembly. ALKBH5 lacking cIDR fails to support paraspeckle formation and NEAT1 stabilization. Phase separation assays, deletion mutants of ALKBH5-cIDR, live-cell imaging of ALKBH5 condensates, m6A demethylation of NEAT1, hypoxia-induced invasion assays The Journal of biological chemistry Medium 37474102
2023 LATS2 kinase phosphorylates ALKBH5, preventing its nuclear export and enhancing its protein stability. Phosphorylated ALKBH5 reciprocally erases m6A from LATS2 mRNA, stabilizing this transcript and establishing a positive feedback loop that promotes glioblastoma stem cell self-renewal. Kinase assay, nuclear fractionation, ALKBH5/LATS2 Co-IP, m6A-seq on LATS2 mRNA, ALKBH5 phosphorylation-site mutants, GBM xenograft models Cell reports Medium 38568805
2025 USP14 deubiquitinase stabilizes ALKBH5 by removing K48-linked ubiquitination through HECW2. MST4 kinase phosphorylates ALKBH5 at S64 and S69, increasing its interaction with USP14 and promoting ALKBH5 deubiquitylation. ALKBH5 also binds and stabilizes USP14 mRNA via YTHDF2-dependent mechanism, creating a positive feedback loop. This MST4-USP14-ALKBH5 axis promotes GSC radioresistance. Mass spectrometry, co-immunoprecipitation, ubiquitination assays, phospho-site mutagenesis (S64/S69), m6A-seq, transcriptome analysis, GSC radioresistance assays, xenograft models Theranostics High 39990235
2021 ALKBH5 demethylates TRAF1 mRNA 3'-UTR, decreasing m6A abundance and enhancing TRAF1 mRNA stability, which promotes TRAF1 protein expression and activates NF-κB and MAPK signaling to drive multiple myeloma cell growth and survival. MeRIP-qPCR, mRNA stability assays, ALKBH5 knockdown in MM cells, in vivo xenograft models, NF-κB/MAPK pathway readouts Oncogene Medium 34759347
2023 ALKBH5 binds and demethylates AXIN2 mRNA, causing AXIN2 mRNA dissociation from IGF2BP1 and subsequent mRNA degradation, resulting in hyperactivated Wnt/β-catenin signaling and induction of DKK1, which recruits myeloid-derived suppressor cells to drive immunosuppression in colorectal cancer. MeRIP-seq, RNA-seq, RIP for IGF2BP1/AXIN2 interaction, ALKBH5 knockin mice (intestine-specific), CD34+ humanized mice, allografts, vesicle-nanoparticle siRNA delivery Gastroenterology High 37169182
2024 ALKBH5 in macrophages demethylates IL-11 mRNA, increasing its stability and IL-11 protein levels, which drives macrophage-to-myofibroblast transition (MMT) under angiotensin II-induced hypertension. Macrophage-specific ALKBH5 knockout inhibits MMT and ameliorates cardiac fibrosis. RIP-seq (identified IL-11 mRNA as target), single-cell transcriptomics, lineage tracing, parabiosis, macrophage-specific ALKBH5 knockout mice, Ang II infusion model, IL-11 overexpression rescue Nature communications High 38443404
2022 ALKBH5 demethylates PKMYT1 mRNA; loss of ALKBH5 increases m6A on PKMYT1 mRNA, and the m6A reader IGF2BP3 stabilizes PKMYT1 mRNA, upregulating PKMYT1 expression and promoting gastric cancer invasion and metastasis. MeRIP-seq, RNA pulldown, mass spectrometry, RIP, ALKBH5 demethylase activity mutant, in vivo lung metastasis model Molecular cancer Medium 35114989
2021 ALKBH5 deficiency in PD-L1 mRNA 3'-UTR enriches m6A modification, promoting YTHDF2-dependent PD-L1 mRNA degradation and reducing tumor PD-L1 expression. ALKBH5 thus sustains PD-L1 expression to promote immune evasion in intrahepatic cholangiocarcinoma. m6A methylome sequencing, ALKBH5-PD-L1 mRNA RIP, YTHDF2 knockdown rescue, in vitro and in vivo ICC tumor models Cancer research Medium 34301762
2020 ALKBH5 deletion in tumor cells modulates Mct4/Slc16a3 mRNA m6A levels and reduces lactate content in the tumor microenvironment, altering infiltration of Treg and myeloid-derived suppressor cells to sensitize tumors to anti-PD-1 immunotherapy. Alkbh5 deletion in tumor cell lines, m6A density analysis, splicing analysis, lactate measurement, flow cytometry of tumor-infiltrating immune cells, small-molecule ALKBH5 inhibitor treatment, in vivo tumor models Proceedings of the National Academy of Sciences of the United States of America Medium 32747553
2022 ALKBH5 mediates m6A demethylation of ITGB1 mRNA in ovarian cancer, suppressing YTHDF2-mediated ITGB1 mRNA degradation and increasing ITGB1 expression, which activates FAK/Src phosphorylation and promotes tumor-associated lymphangiogenesis and lymph node metastasis. Hypoxia induces HIF1α-dependent ALKBH5 upregulation that feeds this pathway. RNA pulldown, RIP-qPCR, Co-IP, MeRIP-qPCR, luciferase reporter assay, in vitro and in vivo lymphangiogenesis models Theranostics Medium 36632222
2022 ALKBH5 mediates m6A demethylation of Drp1 mRNA 3'-UTR. Under low ALKBH5 expression in hepatic stellate cells (HSCs), increased m6A on Drp1 mRNA promotes YTHDF1-mediated translation of DRP1, enhancing mitochondrial fission and HSC proliferation/migration to drive liver fibrosis. MeRIP-qPCR, mRNA stability assays, polysome fractionation, YTHDF1 co-immunoprecipitation, mitochondrial morphology assays, TGF-β1-induced HSC activation, in vivo fibrosis models Pharmacological research Medium 36566000
2022 ALKBH5 demethylates pri-miR-320a-3p, blocking the microprocessor protein DGCR8 from binding and preventing maturation of miR-320a-3p. Reduced mature miR-320a-3p de-represses FOXM1 mRNA (its target), promoting fibroblast activation. ALKBH5 also directly demethylates FOXM1 mRNA in an m6A-dependent manner. RIP assay for DGCR8/pri-miR-320a-3p interaction, MeRIP, miRNA processing assays, ALKBH5 knockdown in fibroblasts, silica-induced pulmonary fibrosis mouse model Cellular & molecular biology letters Medium 35279083
2023 Loss of ALKBH5 increases m6A on OGDH (oxoglutarate dehydrogenase) mRNA, destabilizing it and reducing OGDH protein. Limited OGDH slows the TCA cycle, causing α-KG accumulation and conversion to L-2-HG, which inhibits mitochondrial energy production in hematopoietic stem/progenitor cells and impairs HSPC fitness. Alkbh5 KO mice, m6A-seq, RNA stability assays, metabolomics (α-KG/L-2-HG measurement), HSPC competitive transplantation, human hematopoietic cell in vitro assays Cell reports High 37742191
2023 ALKBH5 erases m6A on CSF3R mRNA (encoding G-CSFR), stabilizing it and increasing G-CSFR surface expression and downstream STAT3 signaling in neutrophils. This drives emergency granulopoiesis and neutrophil mobilization during bacterial sepsis. ALKBH5 direct binding to CSF3R mRNA was confirmed by RIP-qPCR. Alkbh5-deficient mice in CLP sepsis model, RIP-qPCR, m6A quantification of CSF3R mRNA, mRNA stability assays, surface G-CSFR expression, STAT3 signaling readouts Cellular & molecular immunology Medium 38114747
2022 ALKBH5-mediated m6A demethylation of neutrophil migration-related mRNA targets (including CXCR2, NLRP12, PTGER4, TNC, WNK1) imprints a migration-promoting transcriptome in neutrophils. Loss of ALKBH5 reduces CXCR2 expression and impairs neutrophil migration toward CXCL2, increasing mortality in sepsis. Alkbh5-deficient mice in CLP model, CXCR2 surface expression, m6A RNA decay assays, mRNA stability analysis, neutrophil migration assays Signal transduction and targeted therapy Medium 35764614
2022 Loss of ALKBH5 in lymphoid cells increases m6A on Jagged1 and Notch2 mRNAs, reducing their expression and impairing Jagged1/Notch2 signaling. This favors γδ T cell precursor expansion and differentiation, expanding the mature γδ T cell repertoire and enhancing protection against Salmonella infection. Alkbh5 conditional KO in lymphocytes, m6A-seq in thymocytes, flow cytometry of γδ T cell populations, Jagged1/Notch2 expression analysis, Salmonella infection challenge Proceedings of the National Academy of Sciences of the United States of America Medium 35939687
2023 ALKBH5-mediated m6A demethylation ensures timely degradation of maternal RNAs during oocyte meiosis. In Alkbh5-/- oocytes, certain maternal transcripts accumulate with persistent m6A peaks and are recognized by IGF2BP2, stabilizing them and impairing mRNA clearance. Reducing IGF2BP2 in Alkbh5-/- oocytes partially rescues meiotic defects. Alkbh5 knockout female mice, temporal maternal transcriptomics, m6A dynamics profiling, m6A-seq, IGF2BP2 knockdown rescue in Alkbh5-/- oocytes Nature communications High 37848452
2022 ALKBH5 in Sertoli cells regulates m6A modification on Cdh2 mRNA (encoding N-cadherin). Removal of m6A by ALKBH5 promotes Cdh2 mRNA translation via IGF2BP1/2/3 and YTHDF1 complexes, maintaining N-cadherin levels and blood-testis barrier integrity. Alkbh5 knockout mice show disordered basal endoplasmic specialization. m6A-seq, MeRIP-qPCR, RIP-qPCR, Co-IP, polysome fractionation-qPCR, BTB integrity assay, transmission electron microscopy of Alkbh5-KO testes Cellular & molecular biology letters High 36418936
2022 Hypoxia upregulates ALKBH5 in trophoblast cells, which translocates from nucleus to cytoplasm and demethylates SMAD1/SMAD5 mRNAs, enhancing their translation and promoting MMP9 and ITGA1 production to support trophoblast invasion. ALKBH5 knockdown in mouse placenta suppresses trophoblast invasion and causes fetal abortion. m6A-seq in hypoxia-treated trophoblast, nuclear/cytoplasmic fractionation, MeRIP-qPCR, mRNA translation assays for SMAD1/5, trophoblast-specific ALKBH5 knockdown in vivo Biochimica et biophysica acta. Molecular cell research Medium 35724807
2025 ALKBH5 is phosphorylated by protein kinase A (PKA), causing its translocation from nucleus to cytosol in hepatocytes during obesity. Hepatocyte-specific deletion of Alkbh5 reduces glucose and lipids by inhibiting GCGR and mTORC1 signaling pathways. Targeted knockdown of hepatic Alkbh5 reverses T2DM and MAFLD in diabetic mice. PKA phosphorylation assays of ALKBH5, nuclear/cytoplasmic fractionation, hepatocyte-specific Alkbh5 knockout mice, GCGR and mTORC1 pathway analyses, diabetic mouse models Science (New York, N.Y.) High 40014709
2024 PRMT5 directly catalyzes symmetric dimethylation of ALKBH5 at R316. This modification enhances TRIM28-mediated ubiquitination and degradation of ALKBH5, reducing its demethylase activity and increasing m6A on CD276 mRNA, thereby stabilizing CD276 expression and promoting CRC immune evasion. Co-IP, mass spectrometry for meR316, in vitro PRMT5 methylation assay, TRIM28 ubiquitination assay, MeRIP for CD276 mRNA, CRC in vivo models Research (Washington, D.C.) Medium 39781264
2023 ALKBH5-mediated m6A demethylation of JARID2 mRNA stabilizes JARID2 transcripts in cooperation with IGF2BP3, promoting proliferation, migration, and invasion of rheumatoid arthritis fibroblast-like synoviocytes. ALKBH5 knockdown attenuates arthritis severity in CIA and DTHA mouse models. m6A-seq, RNA-seq, RIP, RNA pulldown, ALKBH5 knockdown/overexpression in RA FLSs, CIA/DTHA mouse models with ALKBH5 KO or shRNA injection Arthritis & rheumatology (Hoboken, N.J.) Medium 37584615
2023 ALKBH5 promotes axonal regeneration in dorsal root ganglion neurons by stabilizing Lpin2 mRNA (via m6A demethylation), thereby limiting regenerative lipid metabolism. Knockdown of ALKBH5 enhances sensory axonal regeneration in PNS, and overexpression impairs it in an m6A-dependent manner. In CNS, ALKBH5 knockdown enhances retinal ganglion cell survival and axon regeneration after optic nerve injury. Systematic m6A enzyme screen in axon regeneration, ALKBH5 knockdown and overexpression in rodent DRG neurons, Lpin2 mRNA stability assay, ALKBH5 demethylase-inactive mutant, optic nerve crush model eLife Medium 37535403
2021 ALKBH5 demethylates TFEB mRNA to promote TFEB expression. TFEB in turn transcriptionally activates the ALKBH5 promoter (binding directly to it), while inhibiting METTL3 via mRNA stability downregulation, establishing a positive feedback loop relevant to autophagy regulation. (This is the TFEB→ALKBH5 transcriptional regulation component of PMID 30870073.) ChIP of TFEB at ALKBH5 promoter, luciferase promoter assay, TFEB knockdown/overexpression, mRNA stability of METTL3 Autophagy Medium 30870073
2022 ALKBH5 demethylates CYP1B1 mRNA. In aging MSCs where ALKBH5 is decreased, increased m6A on CYP1B1 mRNA is recognized by IGF2BP1, stabilizing CYP1B1 mRNA, inducing mitochondrial dysfunction and cellular senescence. Alkbh5 knockout in MSCs aggravates spontaneous osteoarthritis. m6A quantification, MeRIP-qPCR for CYP1B1, IGF2BP1 RIP, mitochondrial function assays, Alkbh5 KO mouse spontaneous OA model, MSC senescence assays Experimental & molecular medicine Medium 37524872
2023 ALKBH5 knockdown in NSCLC cells reduces nuclear ALKBH5 distribution via interaction with circEML4 (delivered by extracellular vesicles from M2 macrophages), elevating m6A modifications on SOCS2 mRNA (identified by m6A-seq/RNA-seq), activating the JAK-STAT pathway to promote NSCLC malignancy. circEML4-ALKBH5 interaction assay (Co-IP/RIP), m6A-seq, RNA-seq for SOCS2, nuclear fractionation, EVs transfer assay, in vivo NSCLC xenograft Advanced science Medium 37246269
2024 Astrocytic ALKBH5 demethylates GLT-1 (glutamate transporter-1, SLC1A2) mRNA, increasing GLT-1 expression in astrocytes. Selective deletion of ALKBH5 in astrocytes (but not neurons or endothelial cells) produces antidepressant-like behaviors and preserves stress-induced disruption of glutamatergic synaptic transmission and neuronal integrity in the mPFC. Astrocyte-specific, neuron-specific, and endothelial cell-specific Alkbh5 conditional KO mice, GLT-1 mRNA m6A assay, depression behavioral tests, Ca2+ imaging, synaptic transmission recordings Nature communications High 38773146
2021 ALKBH5 demethylates USP1 mRNA, reducing m6A levels and enhancing USP1 mRNA stability, thereby increasing USP1 expression. USP1 confers glucocorticoid resistance in T-ALL by deubiquitinating Aurora B. ALKBH5 knockdown reduces USP1 and Aurora B, sensitizing cells to dexamethasone. MeRIP-qPCR for USP1 m6A, mRNA stability assays, ALKBH5/USP1 knockdown in T-ALL cells, USP1 rescue experiments, in vivo T-ALL xenograft Molecular carcinogenesis Medium 34169564
2020 ALKBH5 demethylates IGF1R mRNA, enhancing IGF1R mRNA stability and translation, consequently activating IGF1R signaling and promoting endometrial cancer cell proliferation and invasion. MeRIP-qPCR, mRNA stability assays, ALKBH5 knockdown in endometrial cancer cells, IGF1R signaling pathway readouts Journal of Cancer Low 32913456
2025 Psychological stress activates sympathetic nerves to release noradrenaline, which downregulates ALKBH5 in pancreatic cancer cells. ALKBH5 deficiency causes aberrant m6A modification of RNAs, which are packed into extracellular vesicles and delivered to nerves in the tumor microenvironment, enhancing hyperinnervation and PDAC progression. Mouse stress model, ALKBH5 knockdown in PDAC cells, EV m6A RNA profiling, in vivo nerve innervation assays, fisetin treatment to block EV uptake by neurons Nature cell biology Medium 40419796
2020 In cerebral ischemia-reperfusion, Alkbh5 expression increases and, together with FTO, selectively demethylates Bcl2 mRNA, preventing its degradation and enhancing Bcl2 protein expression. Knockdown of Alkbh5 aggravates neuronal damage in this context. Rat MCAO model, primary neuron oxygen deprivation/reoxygenation, Alkbh5 shRNA, m6A quantification, Bcl2 mRNA stability analysis Therapeutic advances in chronic disease Low 32426101
2021 ALKBH5 demethylates Runx2 mRNA, increasing its stability and promoting osteoblast differentiation. Expression of catalytically inactive ALKBH5 (active-site mutant) fails to rescue osteogenesis inhibition caused by ALKBH5 knockdown. ALKBH5 knockdown and overexpression during osteoblast differentiation, catalytic mutant rescue experiment, mRNA stability assay for Runx2 FEBS letters Medium 34105773
2020 TLR4 signaling in the tumor microenvironment activates NF-κB, which upregulates ALKBH5 expression in ovarian cancer cells co-cultured with M2 macrophages. ALKBH5-mediated m6A demethylation increases NANOG mRNA expression, enhancing ovarian cancer aggressiveness. Macrophage-cancer cell co-culture, TLR4/NF-κB pathway inhibitors, transcriptome sequencing, m6A-seq, MeRIP for NANOG mRNA Journal of cellular and molecular medicine Low 32329191
2023 ALKBH5 demethylates and stabilizes DDIT4 mRNA in HNSCC via the RBM33 co-factor (see RBM33 discovery), promoting autophagy and oncogenic function. (This is the downstream functional consequence of ALKBH5-RBM33 complex described in PMID 37257451.) ALKBH5 and RBM33 knockdown in HNSCC, MeRIP for DDIT4, autophagy assays Molecular cell Medium 37257451
2022 ALKBH5 demethylates MAP3K8 mRNA in an m6A-dependent manner, promoting MAP3K8 expression, JNK/ERK pathway activation, IL-8 secretion, and macrophage recruitment in hepatocellular carcinoma. MeRIP-qPCR for MAP3K8 m6A, ALKBH5 knockdown in HCC cells, JNK/ERK pathway readouts, macrophage recruitment assays, single-cell sequencing GSVA International journal of biological sciences Low 35982895
2020 Alkbh5 in mouse neurons is primarily localized to the nucleus, based on immunofluorescence co-localization with NeuN and nuclear markers in adult mouse brain, with expression decreasing dramatically during brain development. Immunofluorescence in adult mouse brain sections and cell lines, co-localization with NeuN and nuclear markers, developmental Western blot Brain research bulletin Low 32717204
2022 ALKBH5 inhibits SAV1 mRNA m6A modification; in ALKBH5-knockdown multiple myeloma cells, increased m6A on SAV1 mRNA decreases SAV1 stability and expression, suppressing HIPPO-pathway signaling and activating YAP, thus exerting an anti-myeloma effect. ALKBH5 also maintains MM stem cell pluripotency. MeRIP-seq for SAV1 m6A, mRNA stability assays, ALKBH5 knockdown in MM cells, HIPPO/YAP pathway readouts, in vivo and in vitro MM models International journal of biological sciences Low 35414790

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Molecular cell 2889 23177736
2017 m6A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program. Cancer cell 1217 28344040
2020 ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment. Proceedings of the National Academy of Sciences of the United States of America 469 32747553
2019 METTL3 and ALKBH5 oppositely regulate m6A modification of TFEB mRNA, which dictates the fate of hypoxia/reoxygenation-treated cardiomyocytes. Autophagy 418 30870073
2020 RNA Demethylase ALKBH5 Selectively Promotes Tumorigenesis and Cancer Stem Cell Self-Renewal in Acute Myeloid Leukemia. Cell stem cell 312 32402250
2020 Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis. Cell stem cell 219 32402251
2022 RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential. Journal of hematology & oncology 212 35063010
2021 Post-translational modification of RNA m6A demethylase ALKBH5 regulates ROS-induced DNA damage response. Nucleic acids research 210 34048572
2022 Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification. Molecular cancer 198 35114989
2021 M6A Demethylase ALKBH5 Regulates PD-L1 Expression and Tumor Immunoenvironment in Intrahepatic Cholangiocarcinoma. Cancer research 198 34301762
2021 ALKBH5 Facilitates Hypoxia-Induced Paraspeckle Assembly and IL8 Secretion to Generate an Immunosuppressive Tumor Microenvironment. Cancer research 192 34670781
2020 The biological function of m6A demethylase ALKBH5 and its role in human disease. Cancer cell international 159 32742194
2020 ALKBH5 Inhibited Cell Proliferation and Sensitized Bladder Cancer Cells to Cisplatin by m6A-CK2α-Mediated Glycolysis. Molecular therapy. Nucleic acids 153 33376625
2023 ALKBH5 Drives Immune Suppression Via Targeting AXIN2 to Promote Colorectal Cancer and Is a Target for Boosting Immunotherapy. Gastroenterology 127 37169182
2020 N6-methyladenosine demethylases Alkbh5/Fto regulate cerebral ischemia-reperfusion injury. Therapeutic advances in chronic disease 118 32426101
2022 ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression. International journal of biological sciences 107 35982895
2024 ALKBH5-mediated m6A modification of IL-11 drives macrophage-to-myofibroblast transition and pathological cardiac fibrosis in mice. Nature communications 97 38443404
2022 ALKBH5-mediated m6A modification of circCCDC134 facilitates cervical cancer metastasis by enhancing HIF1A transcription. Journal of experimental & clinical cancer research : CR 94 36028854
2020 RNA demethylase ALKBH5 promotes ovarian carcinogenesis in a simulated tumour microenvironment through stimulating NF-κB pathway. Journal of cellular and molecular medicine 89 32329191
2022 The m6A demethylase ALKBH5-mediated upregulation of DDIT4-AS1 maintains pancreatic cancer stemness and suppresses chemosensitivity by activating the mTOR pathway. Molecular cancer 79 36056355
2020 N6-methyladenosine ALKBH5 promotes non-small cell lung cancer progress by regulating TIMP3 stability. Gene 79 31927006
2023 Smoking-Induced M2-TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5-Regulated m6A Modification of SOCS2 in NSCLC Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 74 37246269
2023 ALKBH5 activates FAK signaling through m6A demethylation in ITGB1 mRNA and enhances tumor-associated lymphangiogenesis and lymph node metastasis in ovarian cancer. Theranostics 70 36632222
2022 m6A demethylase ALKBH5 is required for antibacterial innate defense by intrinsic motivation of neutrophil migration. Signal transduction and targeted therapy 69 35764614
2023 ALKBH5 facilitates CYP1B1 mRNA degradation via m6A demethylation to alleviate MSC senescence and osteoarthritis progression. Experimental & molecular medicine 68 37524872
2022 ALKBH5 promotes lung fibroblast activation and silica-induced pulmonary fibrosis through miR-320a-3p and FOXM1. Cellular & molecular biology letters 67 35279083
2023 ALKBH5/YTHDF2-mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation. Clinical and translational medicine 65 37381158
2023 EGFR promotes ALKBH5 nuclear retention to attenuate N6-methyladenosine and protect against ferroptosis in glioblastoma. Molecular cell 65 37979586
2022 Mechanisms of substrate recognition and N6-methyladenosine demethylation revealed by crystal structures of ALKBH5-RNA complexes. Nucleic acids research 65 35333330
2024 Insights into the m6A demethylases FTO and ALKBH5 : structural, biological function, and inhibitor development. Cell & bioscience 60 39192357
2024 Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice. Nature communications 56 38773146
2022 ALKBH5 inhibits thyroid cancer progression by promoting ferroptosis through TIAM1-Nrf2/HO-1 axis. Molecular and cellular biochemistry 56 36070054
2022 ALKBH5 attenuates mitochondrial fission and ameliorates liver fibrosis by reducing Drp1 methylation. Pharmacological research 56 36566000
2022 Discovery of a potent, selective and cell active inhibitor of m6A demethylase ALKBH5. European journal of medicinal chemistry 54 35597008
2022 RNA demethylase ALKBH5 regulates hypopharyngeal squamous cell carcinoma ferroptosis by posttranscriptionally activating NFE2L2/NRF2 in an m6 A-IGF2BP2-dependent manner. Journal of clinical laboratory analysis 50 35689537
2023 RBM33 is a unique m6A RNA-binding protein that regulates ALKBH5 demethylase activity and substrate selectivity. Molecular cell 49 37257451
2023 Variant rs8400 enhances ALKBH5 expression through disrupting miR-186 binding and promotes neuroblastoma progression. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 48 37180836
2022 RNA m6A demethylase ALKBH5 regulates the development of γδ T cells. Proceedings of the National Academy of Sciences of the United States of America 48 35939687
2021 RNA demethylase ALKBH5 promotes tumorigenesis in multiple myeloma via TRAF1-mediated activation of NF-κB and MAPK signaling pathways. Oncogene 47 34759347
2023 USP36 promotes tumorigenesis and drug sensitivity of glioblastoma by deubiquitinating and stabilizing ALKBH5. Neuro-oncology 44 36239338
2021 ALKBH5-mediated m6A demethylation of FOXM1 mRNA promotes progression of uveal melanoma. Aging 44 33428593
2025 Liver ALKBH5 regulates glucose and lipid homeostasis independently through GCGR and mTORC1 signaling. Science (New York, N.Y.) 41 40014709
2024 ALKBH5 promotes non-small cell lung cancer progression and susceptibility to anti-PD-L1 therapy by modulating interactions between tumor and macrophages. Journal of experimental & clinical cancer research : CR 41 38872221
2024 Lactylation of RNA m6A demethylase ALKBH5 promotes innate immune response to DNA herpesviruses and mpox virus. Proceedings of the National Academy of Sciences of the United States of America 40 39413129
2020 RNA demethylase Alkbh5 is widely expressed in neurons and decreased during brain development. Brain research bulletin 40 32717204
2020 ALKBH5 regulates IGF1R expression to promote the Proliferation and Tumorigenicity of Endometrial Cancer. Journal of Cancer 40 32913456
2023 ALKBH5 induces fibroblast-to-myofibroblast transformation during hypoxia to protect against cardiac rupture after myocardial infarction. Journal of advanced research 39 37689242
2022 The RNA demethylase ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the stability of the LncRNA PVT1. Cancer cell international 39 36376862
2023 ALKBH5-Mediated RNA m6 A Methylation Regulates the Migration, Invasion, and Proliferation of Rheumatoid Fibroblast-Like Synoviocytes. Arthritis & rheumatology (Hoboken, N.J.) 38 37584615
2023 ALKBH5 modulates hematopoietic stem and progenitor cell energy metabolism through m6A modification-mediated RNA stability control. Cell reports 38 37742191
2023 The RNA m6A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression. Cellular & molecular immunology 38 38114747
2023 RNA demethylase ALKBH5 promotes colorectal cancer progression by posttranscriptional activation of RAB5A in an m6A-YTHDF2-dependent manner. Clinical and translational medicine 36 37203239
2022 ALKBH5 Regulates SPHK1-Dependent Endothelial Cell Angiogenesis Following Ischemic Stress. Frontiers in cardiovascular medicine 36 35127873
2023 ALKBH5-induced circular RNA NRIP1 promotes glycolysis in thyroid cancer cells by targeting PKM2. Cancer science 34 36851875
2023 ALKBH5 controls the meiosis-coupled mRNA clearance in oocytes by removing the N 6-methyladenosine methylation. Nature communications 34 37848452
2022 ALKBH5 in mouse testicular Sertoli cells regulates Cdh2 mRNA translation to maintain blood-testis barrier integrity. Cellular & molecular biology letters 33 36418936
2023 ALKBH5 decreases SLC7A11 expression by erasing m6A modification and promotes the ferroptosis of colorectal cancer cells. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 31 36820954
2024 A covalent compound selectively inhibits RNA demethylase ALKBH5 rather than FTO. RSC chemical biology 30 38576724
2021 ALKBH5-mediated m6A-demethylation of USP1 regulated T-cell acute lymphoblastic leukemia cell glucocorticoid resistance by Aurora B. Molecular carcinogenesis 30 34169564
2024 The demethylase ALKBH5 mediates ZKSCAN3 expression through the m6A modification to activate VEGFA transcription and thus participates in MNNG-induced gastric cancer progression. Journal of hazardous materials 29 38781857
2022 ALKBH5 Promotes Multiple Myeloma Tumorigenicity through inducing m6A-demethylation of SAV1 mRNA and Myeloma Stem Cell Phenotype. International journal of biological sciences 29 35414790
2022 Hypoxia induced ALKBH5 prevents spontaneous abortion by mediating m6A-demethylation of SMAD1/5 mRNAs. Biochimica et biophysica acta. Molecular cell research 29 35724807
2020 ALKBH5 gene polymorphisms and Wilms tumor risk in Chinese children: A five-center case-control study. Journal of clinical laboratory analysis 28 32091154
2023 HPV E7-drived ALKBH5 promotes cervical cancer progression by modulating m6A modification of PAK5. Pharmacological research 27 37480971
2023 Promoting axon regeneration by inhibiting RNA N6-methyladenosine demethylase ALKBH5. eLife 27 37535403
2022 RNA Demethylase ALKBH5 Prevents Lung Cancer Progression by Regulating EMT and Stemness via Regulating p53. Frontiers in oncology 26 35530319
2025 Psychological stress-induced ALKBH5 deficiency promotes tumour innervation and pancreatic cancer via extracellular vesicle transfer of RNA. Nature cell biology 25 40419796
2022 Comparative analysis of the testes from wild-type and Alkbh5-knockout mice using single-cell RNA sequencing. G3 (Bethesda, Md.) 25 35652742
2021 The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability. FEBS letters 25 34105773
2021 m6A demethylase ALKBH5 suppression contributes to esophageal squamous cell carcinoma progression. Aging 25 34491904
2025 KRAS mutants confer platinum resistance by regulating ALKBH5 posttranslational modifications in lung cancer. The Journal of clinical investigation 24 39960727
2024 HSPA4 upregulation induces immune evasion via ALKBH5/CD58 axis in gastric cancer. Journal of experimental & clinical cancer research : CR 23 38589927
2024 Branch Chain Amino Acid Metabolism Promotes Brain Metastasis of NSCLC through EMT Occurrence by Regulating ALKBH5 activity. International journal of biological sciences 23 38993559
2024 Suxiao Jiuxin Pill alleviates myocardial ischemia/reperfusion-induced autophagy via miR-193a-3p/ALKBH5 pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 22 38301300
2023 Bone Lesion-Derived Extracellular Vesicles Fuel Prometastatic Cascades in Hepatocellular Carcinoma by Transferring ALKBH5-Targeting miR-3190-5p. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 22 37096833
2023 ALKBH5-mediated CHAC1 depletion promotes malignant progression and decreases cisplatin-induced oxidative stress in gastric cancer. Cancer cell international 21 38007439
2022 ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway. Open medicine (Warsaw, Poland) 21 35799597
2025 PRMT5-Mediated ALKBH5 Methylation Promotes Colorectal Cancer Immune Evasion via Increasing CD276 Expression. Research (Washington, D.C.) 20 39781264
2025 Lactylation-driven ALKBH5 diminishes macrophage NLRP3 inflammasome activation in patients with G6PT deficiency. The Journal of allergy and clinical immunology 20 39900266
2023 ALKBH5-YTHDF2 m6A modification axis inhibits rheumatoid arthritis progression by suppressing NLRP3. Biochemical and biophysical research communications 20 37244037
2022 m6A RNA, FTO, ALKBH5 Expression in Type 2 Diabetic and Obesity Patients. Journal of the College of Physicians and Surgeons--Pakistan : JCPSP 20 36089710
2025 ALKBH5 suppresses gastric cancer tumorigenesis and metastasis by inhibiting the translation of uncapped WRAP53 RNA isoforms in an m6A-dependent manner. Molecular cancer 19 39815301
2023 The ALKBH5/SOX4 axis promotes liver cancer stem cell properties via activating the SHH signaling pathway. Journal of cancer research and clinical oncology 19 37646828
2025 USP14 modulates stem-like properties, tumorigenicity, and radiotherapy resistance in glioblastoma stem cells through stabilization of MST4-phosphorylated ALKBH5. Theranostics 18 39990235
2023 ALKBH5 promotes hypopharyngeal squamous cell carcinoma apoptosis by targeting TLR2 in a YTHDF1/IGF2BP2-mediated manner. Cell death discovery 18 37612282
2023 YY1 is regulated by ALKBH5-mediated m6A modification and promotes autophagy and cancer progression through targeting ATG4B. Aging 18 37724907
2025 Protein kinase A regulates ferroptosis by controlling GPX4 m6A modification through phosphorylation of ALKBH5. Cell death and differentiation 17 39901038
2025 M6A Demethylase ALKBH5 in Human Diseases: From Structure to Mechanisms. Biomolecules 17 40001461
2025 PRMT5 K240lac confers ferroptosis resistance via ALKBH5/SLC7A11 axis in colorectal cancer. Oncogene 17 40447754
2024 E3 ubiquitin ligase RNF180 mediates the ALKBH5/SMARCA5 axis to promote colon inflammation and Th17/Treg imbalance in ulcerative colitis mice. Archives of pharmacal research 17 39060657
2023 Deubiquitinase USP9X stabilizes RNA m6A demethylase ALKBH5 and promotes acute myeloid leukemia cell survival. The Journal of biological chemistry 16 37454738
2022 ALKBH5 promotes the progression of infantile hemangioma through regulating the NEAT1/miR-378b/FOSL1 axis. Molecular and cellular biochemistry 15 35182329
2025 Discovery of Covalent and Cell-Active ALKBH5 Inhibitors with Potent Antileukemia Effects In Vivo. Angewandte Chemie (International ed. in English) 14 39976119
2024 The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome. PLoS pathogens 14 38227578
2023 The disordered C terminus of ALKBH5 promotes phase separation and paraspeckles assembly. The Journal of biological chemistry 14 37474102
2023 Aging-Associated ALKBH5-m6A Modification Exacerbates Doxorubicin-Induced Cardiomyocyte Apoptosis Via AT-Rich Interaction Domain 2. Journal of the American Heart Association 14 38156523
2024 A LATS2 and ALKBH5 positive feedback loop supports their oncogenic roles. Cell reports 13 38568805
2023 Hypoxia-induced m6A demethylase ALKBH5 promotes ovarian cancer tumorigenicity by decreasing methylation of the lncRNA RMRP. American journal of cancer research 13 37818080
2023 ALKBH5 gene polymorphisms and risk of neuroblastoma in Chinese children from Jiangsu Province. Cancer innovation 13 38946930
2021 ALKBH5 Gene Polymorphisms and Hepatoblastoma Susceptibility in Chinese Children. Journal of oncology 13 33790968

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