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Oncopeptide MBOP Encoded by LINC01234 Promotes Colorectal Cancer through MAPK Signaling Pathway
Chunyuan Tang1, Ying Zhou1, Wen Sun1
1Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Abstract:
Colorectal cancer (CRC) ranks third in incidence rate and second in mortality rate of malignancy worldwide, and the diagnosis and therapeutics of it remain to be further studied. With the emergence of noncoding RNAs (ncRNAs) and potential peptides derived from ncRNAs across various biological processes, we here aimed to identify a ncRNA-derived peptide possible for revealing the oncogenesis of CRC. Through combined predictive analysis of the coding potential of a batch of long noncoding RNAs (lncRNAs), the existence of an 85 amino-acid-peptide, named MEK1-binding oncopeptide (MBOP) and encoded from LINC01234 was confirmed. Mass spectrometry and Western blot assays indicated the overexpression of MBOP in CRC tissues and cell lines compared to adjacent noncancerous tissues and the normal colonic epithelial cell line. In vivo and in vitro migration and proliferation assays defined MBOP as an oncogenic peptide. Immunoprecipitation trials showed that MEK1 was the key interacting protein of MBOP, and MBOP promoted the MEK1/pERK/MMP2/MMP9 axis in CRC. Two E3-ligase enzymes MAEA and RMND5A mediated the ubiquitin-protease-system-related degradation of MBOP. This study indicates that MBOP might be a candidate prognostic indicator and a potential target for clinical therapy of CRC.
Insights
Researchers discovered a new peptide, MEK1-binding oncopeptide (MBOP), derived from LINC01234. MBOP promotes colorectal cancer (CRC) growth and migration, suggesting it as a potential therapeutic target for CRC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Colorectal cancer (CRC) is a leading cause of cancer mortality globally.
- Current diagnostic and therapeutic strategies for CRC require further advancement.
- Noncoding RNAs (ncRNAs) and their derived peptides are emerging as significant players in biological processes.
Purpose of the Study:
- To identify a novel ncRNA-derived peptide involved in colorectal cancer (CRC) oncogenesis.
- To investigate the functional role and molecular mechanisms of the identified peptide in CRC.
Main Methods:
- Bioinformatic analysis to predict coding potential of long noncoding RNAs (lncRNAs).
- Mass spectrometry and Western blot to confirm peptide expression in CRC tissues and cell lines.
- In vitro and in vivo assays to assess migration and proliferation.
- Immunoprecipitation to identify interacting proteins and elucidate signaling pathways.
Main Results:
- An 85-amino-acid peptide, MEK1-binding oncopeptide (MBOP), encoded by LINC01234, was identified.
- MBOP is overexpressed in CRC tissues and cell lines.
- MBOP promotes CRC cell migration and proliferation.
- MBOP interacts with MEK1, activating the MEK1/pERK/MMP2/MMP9 signaling axis.
- MBOP degradation is mediated by E3 ligases MAEA and RMND5A.
Conclusions:
- MBOP functions as an oncogenic peptide in colorectal cancer.
- MBOP may serve as a potential prognostic biomarker for CRC.
- MBOP represents a potential therapeutic target for CRC treatment.
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