ABSTRACT
Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.
ABSTRACT
Background and purpose:The ovarian mucinous tumor is one of the major subtypes of the ovari-an epithelial cancer. Ubiquitination is one of the main post-translational modifications, which has proven to be involved in tumorigenicity. Deubiquitinase is the protein enzyme that could reverse the process of ubiquitination to affect the initiation and progression of malignancies. This study aimed to analyze the expression and clinical application of deubiquitinase OTUB1 (OTU deubiquitinase, ubiquitin aldehyde binding 1) in ovarian primary mucinous tumors. Methods:This study collected 90 cases of ovarian primary mucinous tumors during 2010-2015 in Obstetrics and Gynecology Hospital of Fudan University, and then collected the clinicopathological information and performed the immunochemistry.Results:Fourteen out of 90 cases were ovarian primary mucinous cystadenoma, 17 were borderline mucinous tumor (intestinal type and intraepithelial carcinoma), and 59 were ovarian primary mucinous carcinoma. The expression rate and intensity of OTUB1 were much higher in malignant cases than those in benign ones (P<0.05). The expression rate and intensity of OTUB1 were much higher in cases with mucinous intraepithelial carcinoma than those in cases with intestinal type borderline mucinous tumor (P<0.05). The expression rate and intensity of OTUB1 increased with the advance of FIGO staging (P<0.05). The expression rate and intensity of OTUB1 were much higher in cases with involved fallopian tubes than those in cases without involved fallopian tubes (P<0.05). The expression rate and intensity of OTUB1were much higher in cases with involved uterus and omentum than those in cases with-out involvement (P<0.05). The expression rate and intensity of OTUB1were much higher in cases with lymph node metastasis than those in cases without involvement (P<0.05).Conclusion:There is significant difference in OTUB1 expression between ovarian primary mucinous carcinoma and benign mucinous cystadenoma. It is highly correlated to FIGO staging and invasion and metastasis of tumor. OTUB1 could be used in differential diagnosis and in monitoring the tumor initiation and progression in ovarian mucinous carcinoma.