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Microprotein MP104 Promotes Malignant Progression of Colorectal Cancer Through Regulating Protein Translation
Fang Chen1,2,3, Miao Wang1, Hongmei Yong4
1Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 23, 2026
Summary
Researchers discovered MP104, a microprotein promoting colorectal cancer (CRC) growth and metastasis. MP104 targets the UBE2O-AMPKα2-mTOR-EIF4B pathway, offering a potential biomarker and therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality.
- Identifying novel oncogenic drivers is crucial for effective CRC treatment.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
Purpose of the Study:
- To identify and characterize novel microproteins involved in colorectal cancer pathogenesis.
- To elucidate the molecular mechanisms by which MP104 influences CRC progression.
- To evaluate MP104 as a potential biomarker and therapeutic target for CRC.
Main Methods:
- Discovery and characterization of the microprotein MP104 from ZEB1-AS1.
- In vitro and in vivo functional assays to assess MP104's role in CRC.
- Co-immunoprecipitation and Western blotting to investigate molecular interactions and signaling pathways.
- Analysis of patient data to correlate MP104 expression with CRC prognosis.
Main Results:
- MP104, a microprotein encoded by ZEB1-AS1, is upregulated in CRC and associated with poor prognosis.
- MP104 significantly promotes CRC cell proliferation, migration, invasion, and metastasis.
- MP104 interacts with UBE2O, leading to AMPKα2 degradation and mTOR activation.
- MP104 enhances EIF4B phosphorylation and stability, while inhibiting its ubiquitination, sustaining translational upregulation.
Conclusions:
- MP104 is a novel oncogenic driver in colorectal cancer.
- MP104 promotes CRC progression by reprogramming protein translation via the UBE2O-AMPKα2-mTOR-EIF4B axis.
- MP104 represents a promising biomarker and therapeutic target for colorectal cancer.
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