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

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.

Promotive role of USP29-mediated deubiquitination in malignant proliferation of colorectal cancer cells via the KIAA1429/SOX8 axis

“…Expectedly, the depletion of USP29 effectively limited proliferation of SW620 and HCT116 cells in vitro, and the xenograft tumor models revealed that USP29 downregulation inhibited the proliferation of CRC cells in vivo. In accordance, Chandrasekaran et al has illustrated that silencing USP29 promotes DNA damage and cell apoptosis while hampers cell cycle, potently limiting the growth of CRC cells both in vivo and in vitro [9]. By and large, these findings confirmed the repressive roles of USP29 depletion in the malignant proliferation of CRC cells.…”

The Deubiquitinase USP29 Promotes SARS-CoV-2 Virulence by Preventing Proteasome Degradation of ORF9b

“…The UPS is the primary cytosolic proteolytic machinery for the degradation of various proteins, including viral proteins, whereas viral proteins manipulate host proteins to reverse this process; for instance, the first identified DUB USP7 is associated with viral infection ( 17 , 18 ). USP29 has recently been reported to play an important role in cancer metabolism, progression, and prognosis ( 19 – 22 ). USP29 cooperates with phosphatase SCP1 to stabilize Snail protein, thereby promoting gastric cancer cell migration and mediating HIFα stabilization to induce sorafenib resistance in hepatocellular carcinoma cells by upregulating glycolysis ( 4 ).…”

Application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer

“…Using CRISPR/Cas9 technology to knock out USP29, the cell cycle was prolonged, cell apoptosis was increased, and cell proliferation was inhibited. The high expression of USP29 can promote the occurrence and development of colon cancer and increase its malignant degree ( 58 ).…”