Abstract

<div>Abstract<p>Circular RNAs are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circular RNA. In this study, we found that circMYBL2 in colorectal cancer encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth and aggressiveness of colorectal cancer cells <i>in vitro</i> and <i>in vivo</i>. Mechanistically, p185 counteracted ubiquitin C-terminal hydrolase L3 (UCHL3)–mediated deubiquitination of phosphoglycerate dehydrogenase (PHGDH) by competitively binding to the C1 domain of UCHL3, resulting in PHGDH degradation and a subsequent reduction in serine and glycine biosynthesis. These data revealed that the circMYBL2-encoded p185 isoform serves as a tumor suppressor to inhibit the progression of colorectal cancer by reducing serine biosynthesis.</p><p><b>Significance:</b> A p185 protein encoded by circMYBL2 functions as a tumor suppressor that inhibits the progression of colorectal cancer by increasing the degradation of PHGDH to reduce serine biosynthesis.</p></div>

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