Background: Accumulating evidence shows that N6-methyladenine (m⁶A) modulators contribute to the etiology and progression of colorectal cancer (CRC). However, the exact mechanisms of m⁶A reader involved in glycolytic metabolism remain vague. This article aimed to crosstalk the m⁶A reader with glycolytic metabolism and reveal a new mechanism for the progression of CRC. Methods: The relationship between candidate lncRNA and m⁶A reader was analyzed by bioinformatics, ISH and IHC assays. In vivo and in vitro studies (including MTT, CFA, trans-well, apoptosis, western blot, qRT-PCR and xenograft mouse models) were utilized to explore the biological functions of these indicators. Lactate detection, ATP activity detection and ECAR assays were used to verify the biological function of the downstream target. The bioinformatics, RNA stability, RIP experiments and RNA pull-down assays were used to explore the potential molecular mechanisms. Results: We identified that the crosstalk of the m⁶A reader IMP2 with long-noncoding RNA (lncRNA) ZFAS1 in an m⁶A modulation-dependent manner, subsequently augmented the recruitment of Obg-like ATPase 1 (OLA1) and adenosine triphosphate (ATP) hydrolysis and glycolysis during CRC proliferation and progression. Specifically, IMP2 and ZFAS1 are significantly overexpressed with elevated m⁶A levels in CRC cells and paired CRC cohorts (n = 144). These indicators could be independent biomarkers for CRC prognostic prediction. Notably, IMP2 regulated ZFAS1 expression and enhanced CRC cell proliferation, colony formation, and apoptosis inhibition; thus, it was oncogenic. Mechanistically, ZFAS1 is modified at adenosine +843 within the RGGAC/RRACH element in an m⁶A-dependent manner. Thus, direct interaction between the KH3–4 domain of IMP2 and ZFAS1 where IMP2 serves as a reader for m⁶A-modified ZFAS1 and promotes the RNA stability of ZFAS1 is critical for CRC development. More importantly, stabilized ZFAS1 recognizes the OBG-type functional domain of OLA1, which facilitated the exposure of ATP-binding sites (NVGKST, 32–37), enhanced its protein activity, and ultimately accelerated ATP hydrolysis and the Warburg effect. Conclusions: Our findings reveal a new cancer-promoting mechanism, that is, the critical modulation network underlying m⁶A readers stabilizes lncRNAs, and they jointly promote mitochondrial energy metabolism in the pathogenesis of CRC.

Background: Taraxacum antungense Kitag., a perennial herb belonging to the genus Taraxacum in the family Asteraceae, has been traditionally used as a medicinal plant and is rich in bioactive constituents, including flavonoids and phenolic acids. Previous studies have demonstrated that Taraxacum-derived compounds possess antioxidant, anti-inflammatory, and antitumor activities. However, the anti-melanoma effects and potential cellular mechanisms of flavonoid-enriched extract from T. antungense remain largely unexplored. This study aimed to investigate the anti-melanoma effects of flavonoid-enriched extract from T. antungense and explore the potential mechanisms by integrating phytochemical analysis, network pharmacology, molecular docking, and experimental validation. Methods: Flavonoids in the flowers, leaves, and roots of T. antungense were characterized by UPLC-ESI-MS/MS. Network pharmacology was used to predict candidate bioactive constituents, potential anti-melanoma targets, and associated signaling pathways, and molecular docking was performed to assess predicted ligand–target interactions. The anti-melanoma activity of the flavonoid-enriched extract was evaluated using cell viability, Live/Dead staining, apoptosis, and mitochondrial membrane potential assays. Results: A total of 16 flavonoids were identified across the different organs of T. antungense, with 12 detected in the flowers, 11 in the leaves, and 12 in the roots. Network pharmacology analysis identified 172 potential anti-melanoma targets, with 17 predicted core targets including AKT1, EGFR, BCL2, PTGS2, CDK2, and GSK3B. Enrichment analysis suggested that these targets were mainly associated with cancer-related pathways and apoptosis-related biological processes. Molecular docking suggested favorable predicted interactions between candidate flavonoids (chrysin, luteolin, quercetin, apigenin, and kaempferide) and predicted core targets. In vitro experiments showed that flavonoid-enriched extract from T. antungense inhibited melanoma cell viability in a concentration-dependent manner, induced apoptosis, and induced mitochondrial membrane potential disruption. Conclusions: Our study demonstrates that flavonoid-enriched extract from T. antungense exerts anti-melanoma effects by suppressing melanoma cell viability and promoting apoptosis accompanied by mitochondrial membrane potential disruption. Network pharmacology and molecular docking further suggest that multiple targets and signaling pathways may contribute to these effects.