The circMYBL2-Encoded p185 Protein Suppresses Colorectal Cancer Progression by Inhibiting Serine Biosynthesis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in various cancers.
• Previous research identified circMYBL2 as a tumor-promoting circRNA in cancer.
• The functional and mechanistic roles of circRNAs, particularly protein-coding potential, are areas of active investigation.

Purpose of the Study:

• To investigate the functional role of circMYBL2 in colorectal cancer.
• To identify and characterize any protein encoded by circMYBL2.
• To elucidate the molecular mechanism by which circMYBL2 influences colorectal cancer progression.

Main Methods:

• Identification and characterization of a novel protein (p185) encoded by circMYBL2.
• In vitro and in vivo assays to assess the effect of p185 on colorectal cancer cell growth and aggressiveness.
• Mechanistic studies involving protein-protein interactions, ubiquitination assays, and metabolic pathway analysis (serine and glycine biosynthesis).

Main Results:

• CircMYBL2 encodes a 185-amino acid protein, p185.
• p185 demonstrated tumor-suppressive activity, inhibiting colorectal cancer cell growth and aggressiveness both in vitro and in vivo.
• Mechanistically, p185 counteracts UCHL3-mediated PHGDH deubiquitination by binding to UCHL3, leading to PHGDH degradation and reduced serine/glycine biosynthesis.

Conclusions:

• The circMYBL2-encoded p185 protein functions as a tumor suppressor in colorectal cancer.
• p185 inhibits colorectal cancer progression by targeting the serine biosynthesis pathway via PHGDH degradation.
• These findings reveal a novel tumor-suppressive role for a circRNA-encoded protein and highlight a new mechanism in colorectal cancer regulation.