Histone Lactylation Mediated by circRNA-Facilitated FXR1 Phase Separation Promotes Colorectal Cancer Progression.

circ2891 is aberrantly upregulated in colorectal cancer tumors and is linked to poor patient outcomes, while driving histone lactylation through FXR1 phase separation.

• Why it matters: Tumors can couple metabolism to epigenetic programs via lactate-driven histone lactylation, but how this is coordinated in colorectal cancer remains unclear.
• What they did: The study identified circ2891 as a metabolic and lactylation driver, showing it boosts aerobic glycolysis and lactate production; mechanistically, circ2891 binds FXR1 to promote phase separation that stabilizes PGK1 and ENO1 mRNAs.
• The result: Increased PGK1/ENO1 elevates histone lactylation, which transcriptionally activates DDX21 to promote colorectal cancer progression, and dual targeting of circ2891 and histone lactylation suppresses patient-derived organoid and xenograft growth.

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