By Daniel Walocha ‘19
Colorectal cancer (CRC) is the third leading cause of cancer death. Metastasis is one of the largest determinants of survival for colorectal cancer; treatment before metastasis is crucial for survival. Targeting potential gene products that promote proliferation and invasion could reduce cancer metastasis and growth. TRIM25 is an E3 ubiquitin ligase found to be responsible for the polyubiquitination of retinoic acid inducible gene (RIG-1) and is required for melanoma differentiation associated gene 5 (MDA5). It has been most recently proposed that TRIM25 positively regulates Transforming growth factor beta (TGF-B) signaling in CRC.
Dr. Nianfeng Sun from Shandong University analyzed TRIM25’s role in TGF-B signaling in CRC. TGF-B is a cytokine belonging to a superfamily of transforming growth factors that are involved in cell signaling leading to proliferation and differentiation. Dr. Sun utilized HCT116 and HT29 CRC cell lines that were transfected with TRIM25 plasmids to overexpress the gene. Cells were implanted in mice for in vivo analysis of migration. A western blot was used to determine TGF-B signaling target expression. It was found that Smad2 and Smad4, both downstream TGF-B signaling targets, were overexpressed in conjunction with TRIM25 overexpression. The mice were found to have increased cancer migration following implantation of HCT116 and HT29 CRC with increased TRIM25 expression, measured by a wound healing assay.
It is concluded from this experiment that TRIM25 is an oncogene in CRC that upregulates the TGF-B pathway, as shown through western blotting and migration assays. Future experiments should work to inhibit TRIM25 expression via RNAi or find signaling molecules that inhibit its expression.
- N. Sun, et al. Tripartite motif containing 25 promotes proliferation and invasion of colorectal cancer cells through TGF-β signaling. Bioscience Reports 4, (2017). doi: 10.1042/BSR20170805.
- Image retrieved from: https://commons.wikimedia.org/wiki/File:Protein_TGFB1_PDB_1kla.png