Abstract
Simple SummaryAmong 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.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.
Highlights
Colorectal carcinoma (CRC) is the third most common form of cancer among males and the second-most commonly diagnosed cancer in females
We found that Ubiquitin-specific protease 29 (USP29) was highly upregulated in colon cancer tissue when compared to its corresponding normal tissue (Figure 1B)
USP29 overexpression significantly increased cell proliferation, Cancers 2021, 13, 2706 compared with the vector controls, in HCT116 and SW480 cells (p = 0.001 and p = 0.0004, Cancers 2021, 13, x FOR PEER REVIEWrespectively) (Figure 2D,E). These findings suggest that USP29 could be an oncogen3eoaf n1d4 promotes the proliferation of colon cancer
Summary
Colorectal carcinoma (CRC) is the third most common form of cancer among males and the second-most commonly diagnosed cancer in females. DUBs control the expression, localization, and activity of numerous proteins and participate in various cellular processes, including the growth, cell cycle, signal transduction, and apoptosis [3,4]. DUBs play a crucial role in cancer initiation and progression [7]. Accumulating evidence suggests that DUBs play a prominent role in tumorigenesis at multiple levels [8]. 100 DUBs that regulate different functions have been reported in humans, and they are expressed in various tissues and organs. USPs contain different functional domains, such as zinc finger and ubiquitin-binding motifs, indicating that each USP can cooperate with different proteins and be involved in unique cellular processes [10]. It has been reported that the altered expression and mutation of USPs are closely linked with various human cancers [7]
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