Ubiquitin Specific Protease 29 Functions as an Oncogene Promoting Tumorigenesis in Colorectal Carcinoma

SIMPLE SUMMARY: Among other cancers, colorectal carcinoma (CRC) is one of the foremost causes of death worldwide. The mortality rate of those having CRC has increased dramatically in the past few years. Identification of novel regulatory molecules contributing to the progression of CRC remains a focus of significant interest. The oncogenic role of USP29 has recently been explored in a few cancer types. However, evidence concerning the expression of USP29 in other cancers is currently lacking. We identified that USP29 is highly expressed in CRC and may contribute to the progression of CRC. Depletion of USP29 in HCT116 by CRISPR-Cas9 system reduced the growth of cancer cells. Furthermore, our data suggests that USP29 knockdown reduced the tumor volume of mouse xenograft models. Future investigations are required to validate the outcome of USP29-targted therapy in patients having CRC. ABSTRACT: Colorectal carcinoma is the third foremost cause of cancer-related deaths and accounts for 5.8% of all deaths globally. The molecular mechanisms of colon cancer progression and metastasis control are not well studied. Ubiquitin-specific protease 29 (USP29), a deubiquitinating enzyme, is involved in the occurrence and development of wide variety of cancers. However, its clinical significance and biological roles in colorectal carcinoma (CRC) remain unexplored. In this research, we observed that the rate of USP29 overexpression was higher in colon cancer patient tissues relative to its corresponding normal tissues. CRISPR-Cas9-mediated depletion of USP29 triggered DNA double strand breaks and delayed cell-cycle progression in HCT116 cells. We also demonstrated that USP29 depletion hampers the colony formation and increases apoptosis of HCT116 cells. USP29 knockdown significantly decreased CRC cell proliferation in vitro. Depletion of USP29 in HCT116 cells substantially reduced the tumor volume of mouse xenografts. In conclusion, our study shows that elevated expression of USP29 promotes malignancy in CRC, suggesting that USP29 could be a promising target for colon cancer therapy.