A Novel Microprotein, MUCP1, Mediates Succinate Transport and Promotes Colorectal Cancer Progression by Modulating Glutamine Metabolism
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. Overall design: This RNA-seq dataset examines the transcriptomic impact of MUCP1 overexpression in SW480 colorectal cancer cells. The experiment includes two groups: control (LV-NC) and MUCP1-FLAG overexpression. RNA was extracted from biological replicates of both groups for sequencing, with the aim of identifying differentially expressed genes influenced by elevated MUCP1 levels. Comparative gene expression analysis and pathway enrichment studies were conducted to assess changes, particularly in metabolic and signaling pathways.