Epigenetic inactivation of the candidate tumor suppressor<i>USP44</i>is a frequent and early event in colorectal neoplasia

Sloane, Mathew A.; Wong, Jason; Perera, D. S.; Nunez, Andrea C.; Pimanda, John E.; Hawkins, Nicholas J.; Sieber, Oliver M.; Bourke, Michael J.; Hesson, Luke B.; Ward, Robyn L.

doi:10.4161/epi.29222

Cited by 37 publications

(33 citation statements)

References 19 publications

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“…In lung adenocarcinomas, USP44 mRNA expression levels are reduced and correlate with poor prognosis (5). It has recently been shown that USP44 is inactivated by hypermethylation in colorectal adenomas, but such epigenetic inactivation is not associated with aneuploidy in colorectal neoplasia (17). This last finding is in line with the study results.…”

Section: Discussionsupporting

confidence: 83%

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

et al. 2017

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Chromosomal instability, leading to aneuploidy, is one of the hallmarks of human cancers. USP44 (ubiquitin specific peptidase 44) is an important molecule that plays a regulatory role in the mitotic checkpoint and USP44 loss causes chromosome missegregation, aneuploidy and tumorigenesis in vivo. In this study, it was investigated the immunoexpression of USP44 in 28 malignant salivary gland neoplasms and associated the results with DNA ploidy status assessed by image cytometry. USP44 protein was widely expressed in most of the tumor samples and no clear association could be established between its expression and DNA ploidy status or tumor size. On this basis, it may be concluded that the aneuploidy of the salivary gland cancers included in this study was not driven by loss of USP44 protein expression.

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Section: Discussionsupporting

confidence: 83%

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

et al. 2017

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“…However, because of nonspecific symptoms in the early stage and lack of effective diagnostic biomarkers, a low early diagnostic rate brings challenges for effective treatment. Abnormal methylation biomarkers have proven to be useful in diagnosing numerous cancers [102,103]. In the current study, the results demonstrated that the combined sensitivity, specificity, and AUC values of CDKN2A methylation were 0.36, 0.96, and 0.77, respectively, indicating that detection of CDKN2A promoter methylation has a moderate diagnostic accuracy for HNSCC.…”

Section: Discussionmentioning

confidence: 62%

The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

Zhou

Shen

et al. 2018

Cell Physiol Biochem

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Background/Aims: The association between cyclin-dependent kinase inhibitor 2A (CDKN2A) hypermethylation and head and neck squamous cell carcinoma (HNSCC) risk has been investigated by a number of studies. However, these studies have not demonstrated consistent results. Moreover, the role of CDKN2A methylation in HNSCC carcinogenesis and its clinical significance remain unclear. Methods: We performed a systematic meta-analysis based on 72 articles (including 3399 HNSCCs, 668 premalignant lesions, and 2393 normal controls) from the PubMed, Google Scholar, Web of Science, Embase, China National Knowledge Infrastructure and Wanfang databases. Results: Our study showed a significant increase in the frequency of CDKN2A methylation during HNSCC carcinogenesis (HNSCC vs. normal controls, odds ratio (OR) = 6.72, P < 0.01; HNSCC vs. precancerous lesions, OR = 1.89, P < 0.05; precancerous lesions vs. normal controls, OR = 14.70, P < 0.01). Moreover, CDKN2A methylation was significantly associated with gender (OR = 1.34; P < 0.05) and lymph node metastasis (OR = 2.32; P < 0.01). The area under summary receiver operating characteristic curve (AUC) for diagnosis of HNSCC based on all samples and saliva sample subgroup were 0.77 and 0.96, respectively. Additionally, CDKN2A hypermethylation was significantly associated with shorter overall survival (OS) (hazard ratio (HR) = 1.01, P < 0.05) and recurrence-free survival (RFS) (HR = 1.77, P < 0.05). Conclusion: Our findings indicate CDKN2A methylation is involved in the carcinogenesis, progression, and metastasis of HNSCC. Furthermore, methylated CDKN2A could be a potential diagnostic and prognostic biomarker for HNSCC.

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“…A recent article reported that USP44 and other several genes showed prior evidence of a tumor suppressive function by the pan‐cancer analysis . Another article also showed that loss of USP44 was associated with aneuploidy and cancer in mouse models, and USP44 was also transcriptionally silenced in human cancers . And it also showed that USP44 was epigenetically inactivated in colorectal adenomas, and epigenetic inactivation of the candidate tumor suppressor USP44 was a frequent and early event in colorectal neoplasia .…”

Section: Discussionmentioning

confidence: 93%

“…GAPDH was used as an internal control and USP44 was also transcriptionally silenced in human cancers. 27 And it also showed that USP44 was epigenetically inactivated in colorectal adenomas, and epigenetic inactivation of the candidate tumor suppressor USP44 was a frequent and early event in colorectal neoplasia. 27 Previous study also reported that the DUB USP44 was a tumor suppressor that protected against chromosome missegregation.…”

Section: Discussionmentioning

confidence: 99%

“…27 And it also showed that USP44 was epigenetically inactivated in colorectal adenomas, and epigenetic inactivation of the candidate tumor suppressor USP44 was a frequent and early event in colorectal neoplasia. 27 Previous study also reported that the DUB USP44 was a tumor suppressor that protected against chromosome missegregation. 28,29 However, USP44 has been also implicated in tumor progression and metastasis across several tumors.…”

Section: Discussionmentioning

confidence: 99%

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Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer

Zhang

Wang

Zhang

et al. 2019

The Kaohsiung J of Med Scie

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Ubiquitin‐specific protease 44 (USP44) has been reported as a tumor suppressor or promoter in some tumors, but its function in non‐small cell lung cancer (NSCLC) is still unclear. In this study, USP44 was found significantly downregulated in both of NSCLC tissues and cell lines, and low expression of USP44 predicted a poor prognosis for NSCLC patients. Overexpression of USP44 markedly downregulated the expression levels of Cyclin D1 and CDK4, but upregulated p53 expression, as a result of which, suppressing the cell growth of NSCLC cells. Further studies indicated that overexpression of USP44 significantly inhibited the phosphorylation of AKT, and its down‐stream signals, including mTOR and P70S6K. Moreover, overexpression of USP44 increased PTEN protein but not its mRNA levels, which suggested that USP44 inhibited AKT signaling by stabilizing PTEN in NSCLC cells. In conclusion, we demonstrated that USP44 showed prior evidence of a tumor suppressive function in NSCLC cells, and inhibited NSCLC cell growth by suppressing AKT signaling, suggesting that USP44 could be as a novel target for NSCLC therapy.

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Epigenetic inactivation of the candidate tumor suppressorUSP44is a frequent and early event in colorectal neoplasia

Cited by 37 publications

References 19 publications

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

DNA Aneuploidy in Malignant Salivary Gland Neoplasms is Independent of USP44 Protein Expression

The Association and Clinical Significance of CDKN2A Promoter Methylation in Head and Neck Squamous Cell Carcinoma: a Meta-Analysis

Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer

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