ArticleCell & bioscience2023
Down-regulated FTO and ALKBH5 co-operatively activates FOXO signaling through m6A methylation modification in HK2 mRNA mediated by IGF2BP2 to enhance glycolysis in colorectal cancer.
Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 61 citations in OpenAlex.
- The role, regulatory mechanisms, and therapeutic implications of FTO in gastrointestinal cancer.Genes & diseases · 2026Review
- Article
- Glycolytic reprogramming in endometriosis: molecular mechanisms, immune modulation, and non-hormonal therapeutic opportunities.BMC women's health · 2026Review
- mInternational journal of molecular medicine · 2026Review
- NNature reviews. Cancer · 2026Review
- The AHCY-adenosine complex rewires mRNA methylation to enhance fatty acid biosynthesis and tumorigenesis.Cell research · 2026Article
- FTO-mediated m6A demethylation of CSF3 suppresses NETosis via downregulation of RLN2 expression in colorectal cancer.Cell biology and toxicology · 2026Article
- Identification of Key Sequence Motifs Essential for the Recognition of mBiomolecules · 2026Article
- Reader-dependent functional duality of FTO: a context-switching node at the intersection of immune evasion and therapeutic resistance.Frontiers in immunology · 2026Review
- The spatiotemporal dynamic evolution of post-stroke neuroinflammation: energy metabolism mechanisms of acute response and chronic progression.Frontiers in pharmacology · 2026Review
- mFrontiers in cell and developmental biology · 2026Review
- Metabolic reprogramming-associated genomic instability drives colorectal cancer progression via the UBXN1-NF-κB axis.American journal of translational research · 2026Article
- Crosstalk between mFrontiers in immunology · 2026Review
- Mitochondria at the intersections of RNA modifications and metabolism reprogramming implications in cell death, tumor microenvironment, and immunotherapy.Journal of hematology & oncology · 2025Review
- Review
- Fat mass and obesity-associated protein downregulation enhances N6-methyladenosine methylation and drives ovarian cancer progression.Journal of cell communication and signaling · 2025Article
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- METTL3 in colorectal cancer: molecular insights and clinical implications.Molecular biology reports · 2025Review
- The Clinical Relevance of FTO as a Demethylase Beyond Cancer: Molecular Mechanisms and Therapeutic Opportunities.Aging and disease · 2025Review
- Crosstalk between lactylation and RNA modifications in tumorigenesis: mechanisms and therapeutic implications.Biomarker research · 2025Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundN6-methyladenosine (m6A) modification is the most abundant reversible methylation modification in eukaryotes, and it is reportedly closely associated with a variety of cancers progression, including colorectal cancer (CRC). This study showed that activated lipid metabolism and glycolysis play vital roles in the occurrence and development of CRC. However, only a few studies have reported the biological mechanisms underlying this connection.
methodsProtein and mRNA levels of FTO and ALKBH5 were measured using western blot and qRT-PCR. The effects of FTO and ALKBH5 on cell proliferation were examined using CCK-8, colony formation, and EdU assays, and the effects on cell migration and invasion were tested using a transwell assay. m6A RNA immunoprecipitation (MeRIP) and RNA-seq was used to explore downstream target gene. RIP was performed to verify the interaction between m6A and HK2. The function of FTO and ALKBH5 in vivo was determined by xenograft in nude mice.
resultsIn this study, FTO and ALKBH5 were significantly down-regulated in CRC patients and cells both in vivo and in vitro in a high-fat environment. Moreover, FTO and ALKBH5 over-expression hampered cell proliferation both in vitro and in vivo. Conversely, FTO and ALKBH5 knockdown accelerated the malignant biological behaviors of CRC cells. The mechanism of action of FTO and ALKBH5 involves joint regulation of HK2, a key enzyme in glycolysis, which was identified by RNA sequencing and MeRIP-seq. Furthermore, reduced expression of FTO and ALKBH5 jointly activated the FOXO signaling pathway, which led to enhanced proliferation ability in CRC cells. IGF2BP2, as a m6A reader, positively regulated HK2 mRNA in m6A dependent manner. Additionally, down-regulation of FTO/ALKBH5 increased METTL3 and decreased METTL14 levels, further promoting CRC progression.
conclusionIn conclusion, our study revealed the FTO-ALKBH5/IGF2BP2/HK2/FOXO1 axis as a mechanism of aberrant m6A modification and glycolysis regulation in CRC.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.