BACKGROUND AND AIMS: Increasing experimental evidence suggests that ubiquitin-specific protease 22 (USP22) could exhibit a critical function in pathological processes, including oncogenesis and cell cycle progression. The aim of this study was to investigate the role of USP22 and the association with its potential targets in colorectal cancer (CRC). METHODS: We evaluated the implication of USP22 and the candidate targets, such as B-cell-specific murine leukemia virus integration site-1 (BMI-1), cellular homolog of avian myelocytomatosis virus oncogene (c-Myc), cyclin D2, inhibitor of cyclin-dependent kinase (CDK) 4 (p16INK4a), and an alternate reading frame product of the CDKN2A locus (p14ARF), in matched samples comprising carcinoma and adjacent non-cancerous mucosa from 82 patients with CRC using quantitative reverse transcription-polymerase chain reaction and immunostaining analyses. RESULTS: The USP22 mRNA expression in the CRC tissues was significantly higher than those in the non-cancerous mucosa tissues (P < 0.0001). Increased mRNA expression of USP22 was associated with advanced American Joint Committee on Cancer stage (P = 0.033) and high likelihood of therapy failure after radical resection (P < 0.0001). The Cox regression analysis revealed that the USP22 mRNA expression level was a significant factor for predicting prognosis (P < 0.0001). The statistical correlation analysis in mRNA levels showed that USP22 was strongly correlated with BMI-1 (r = 0.790, P < 0.0001), c-Myc (r = 0.528, P < 0.0001), and cyclin D2 (r = 0.657, P < 0.0001), but not p16INK4a (r = 0.103, P = 0.358) or p14ARF (r = -0.039, P = 0.731). CONCLUSION: Our results indicate that activation of USP22 correlates with CRC progression and therapy failure. Additionally, the oncogenic role of USP22 in the progression of CRC can be mechanistically linked with BMI-1, c-Myc, and cyclin D2, but not with p16INK4a and p14ARF.
BACKGROUND AND AIMS: Increasing experimental evidence suggests that ubiquitin-specific protease 22 (USP22) could exhibit a critical function in pathological processes, including oncogenesis and cell cycle progression. The aim of this study was to investigate the role of USP22 and the association with its potential targets in colorectal cancer (CRC). METHODS: We evaluated the implication of USP22 and the candidate targets, such as B-cell-specific murine leukemia virus integration site-1 (BMI-1), cellular homolog of avian myelocytomatosis virus oncogene (c-Myc), cyclin D2, inhibitor of cyclin-dependent kinase (CDK) 4 (p16INK4a), and an alternate reading frame product of the CDKN2A locus (p14ARF), in matched samples comprising carcinoma and adjacent non-cancerous mucosa from 82 patients with CRC using quantitative reverse transcription-polymerase chain reaction and immunostaining analyses. RESULTS: The USP22 mRNA expression in the CRC tissues was significantly higher than those in the non-cancerous mucosa tissues (P < 0.0001). Increased mRNA expression of USP22 was associated with advanced American Joint Committee on Cancer stage (P = 0.033) and high likelihood of therapy failure after radical resection (P < 0.0001). The Cox regression analysis revealed that the USP22 mRNA expression level was a significant factor for predicting prognosis (P < 0.0001). The statistical correlation analysis in mRNA levels showed that USP22 was strongly correlated with BMI-1 (r = 0.790, P < 0.0001), c-Myc (r = 0.528, P < 0.0001), and cyclin D2 (r = 0.657, P < 0.0001), but not p16INK4a (r = 0.103, P = 0.358) or p14ARF (r = -0.039, P = 0.731). CONCLUSION: Our results indicate that activation of USP22 correlates with CRC progression and therapy failure. Additionally, the oncogenic role of USP22 in the progression of CRC can be mechanistically linked with BMI-1, c-Myc, and cyclin D2, but not with p16INK4a and p14ARF.
Authors: Jennifer J McCann; Irina A Vasilevskaya; Neermala Poudel Neupane; Ayesha A Shafi; Christopher McNair; Emanuela Dylgjeri; Amy C Mandigo; Matthew J Schiewer; Randy S Schrecengost; Peter Gallagher; Timothy J Stanek; Steven B McMahon; Lisa D Berman-Booty; William F Ostrander; Karen E Knudsen Journal: Cancer Res Date: 2019-11-18 Impact factor: 12.701
Authors: Huadong Zhao; Haili Tang; Qike Huang; Bo Qiu; Xiaomin Liu; Dong Fan; Li Gong; Hang Guo; Chong Chen; Shixiong Lei; Lu Yang; Jianguo Lu; Guoqiang Bao Journal: Am J Cancer Res Date: 2016-11-01 Impact factor: 6.166