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A Novel Microprotein, MUCP1, Mediates Succinate Transport and Promotes Colorectal Cancer Progression by Modulating Glutamine Metabolism

ABSTRACT: Metabolic reprogramming is a hallmark of colorectal cancer (CRC) progression, yet the molecular mechanisms governing this process remain largely unresolved. And the translational roles of numerous long non-coding RNAs (lncRNAs) have been largely overlooked, despite their protein products being essential in cancer progression. This study identifies MUCP1, the microprotein encoded by lncRNA MUC20-OT1, as a central regulator of metabolic processes in CRC. Positioned on the mitochondrial outer membrane, MUCP1 is vital for the export of succinate, a key oncometabolite. Acute depletion of MUCP1 causes succinate accumulation, Tricarboxylic acid cycle (TCA) instability, and disruptions in glutamine metabolism. Cancer cells lacking MUCP1 show decreased H3K4me3 modifications on genes crucial for glutamine metabolism, driving further metabolic imbalance. Sustained MUCP1 deficiency ultimately triggers metabolic reprogramming, emphasizing the role of this microprotein in linking mitochondrial metabolism to epigenetic regulation and presenting it as a promising therapeutic target in CRC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE281816 | GEO | 2025/10/31

REPOSITORIES: GEO

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A Novel Microprotein, MUCP1, Mediates Succinate Transport and Promotes Colorectal Cancer Progression by Modulating Glutamine Metabolism

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