# UBE2M as a bridge spanning neddylation and cell cycle regulation in colorectal adenocarcinoma

## TL;DR

This study shows that UBE2M links the neddylation process to cell cycle control in colorectal cancer, and targeting it with micafungin may help treat the disease.

## Contribution

UBE2M is identified as a novel bridge between neddylation and cell cycle regulation in colorectal cancer.

## Key findings

- UBE2M promotes CRC progression by neddylating USP39 and modulating PABPC1.
- Micafungin inhibits UBE2M and suppresses CRC progression in mice.
- Neddylation is associated with G2M phase progression in colorectal cancer.

## Abstract

Protein neddylation is a post-translational modification process that modifies the functional state of proteins by conjugating NEDD8, a ubiquitin-like polypeptide, to the lysine residues of substrates. In various cancers, neddylation is upregulated and implicated in cancer progression via modulating cell cycle-related proteins. However, in colorectal cancer (CRC), the relationship between neddylation and the cell cycle remains incompletely understood. Here, by leveraging single-cell and bulk transcriptome data, we demonstrated that neddylation is associated with G2M phase progression in CRC. Through bioinformatic analysis, we identified ubiquitin conjugating enzyme E2 M (UBE2M) as a molecular bridge spanning neddylation and the cell cycle in CRC. To elucidate how UBE2M promotes CRC progression, we conducted in vivo and in vitro experiments to confirm the role of UBE2M in neddylating USP39, which in turn modulates the deubiquitination of PABPC1, enhances the translation efficiency of CCNB1 and propels the cell cycle progression of CRC. Regarding clinical application, we identified micafungin as an inhibitor of UBE2M capable of suppressing the regulatory axis and, consequently, hindering CRC progression. Therefore, this study underscores the potential role of UBE2M in bridging neddylation with the cell cycle and holds promise for advancing targeted therapies in CRC treatment.

Colorectal cancer is a major health concern worldwide, being the third most common and second deadliest cancer. This study explores a process called neddylation, which modifies proteins to control their function and stability, in colorectal cancer. The researchers focused on a protein called UBE2M, which is involved in neddylation and may play a role in cancer progression. The team used advanced techniques to analyze cancer cells from patients, identifying that UBE2M is overexpressed in colorectal cancer tissues. They found that UBE2M helps cancer cells grow by stabilizing another protein, PABPC1, which is crucial for cell cycle progression. By inhibiting UBE2M with a drug called micafungin, they were able to slow down tumor growth in mice. The study concludes that targeting UBE2M could be a promising strategy for treating colorectal cancer.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.