The deubiquitinase OTUB2 promotes cervical cancer growth through stabilizing FOXM1.

OBJECTIVES: Ovarian tumor (OTU) domain-containing ubiquitin aldehyde-binding protein Otubain2 (OTUB2) is an important cysteine protease with deubiquitinase activity in the OTU family. However, the role of OTUB2 in cervical cancer (CC) has not been investigated. METHODS: OTUB2 expression was analyzed employing the CC data from The Cancer Genome Atlas (TCGA) database. Western blot and qRT-PCR analysis were performed to identify OTUB2 expression in CC. The oncogenic function of OTUB2 was identified through a series of in vitro and in vivo experiments. Tandem Mass Tag™ Quantitative Proteomics examination was used to identify potential targets of OTUB2. RESULTS: OTUB2 was overexpressed in CC and was related to poor prognosis of patients. In our in-house cohort, we also showed that OTUB2 was overexpressed in tumor tissues of CC compared to para-tumor. Knockdown of OTUB2 suppressed CC cell growth whereas OTUB2 upregulation fostered the proliferation of cancer cells. Forkhead box M1 (FOXM1) was found to be a target of OTUB2. FOXM1 can be positively regulated by OTUB2 in CC cells. In human CC tissues, protein level of FOXM1 was positively correlated with OTUB2. FOXM1 was found to play a critical role in OTUB2-mediated CC cell growth. Mechanistically, OTUB2 could bind FOXM1 and deubiquitinate FOXM1 to stabilize it. CONCLUSION: OTUB2 promotes CC progression through deubiquitinating and stabilizing FOXM1.

Pelvic metastatic squamous cell carcinoma of unknown primary site: A case report and brief literature review.

RATIONALE: Cancer with unknown primary site is a kind of disease that is difficult to deal with clinically, accounting for 2% to 9% of all newly diagnosed cancer cases. Here, we report such a case with pelvic metastatic squamous cell carcinoma of an unknown primary site and review the relevant literature. PATIENT CONCERNS DIAGNOSES: A 43-year-old Chinese female patient was referred to our hospital and initially diagnosed as "malignant tumor of right adnexal area?, obstruction of right ureter, secondary hydronephrosis". INTERVENTIONS: Thereafter cytoreductive surgery was performed which included a total hysterectomy, left adnexectomy, partial omentum resection, pelvic lymph node dissection, and para-aortic lymph node dissection. The primary lesion could not be identified by supplementary examination and postoperative pathology. The patient was diagnosed as pelvic metastatic squamous cell carcinoma whose primary site was unknown. To prevent a recurrence, we administered adjuvant chemotherapy for the patient. OUTCOMES: The patient was followed up after treatment, complete remission has been maintained for 72 months, and no recurrence or metastasis has been found. LESSONS: Our case demonstrates that surgery combined with chemotherapy could be helpful for pelvic metastatic squamous cell carcinoma of unknown primary site.

DJ-1 activates the noncanonical NF-κB pathway via interaction with Cezanne to inhibit the apoptosis and promote the proliferation of Ishikawa cells.

BACKGROUND: Endometrial cancer is generally one of the most evident malignant tumours of the female reproductive system, and the mechanisms underlying its cell proliferation and apoptosis are key to research in gynaecological oncology. In the paper, the in-depth molecular mechanism by which DJ-1 protein regulates the proliferation and apoptosis of Ishikawa cells was investigated. METHODS AND RESULTS: DJ-1 knockdown and overexpressing Ishikawa stable cell lines were established by lentiviral transduction. The levels of DJ-1 and noncanonical NF-κB signaling key proteins were evaluated by Western blotting. Cell counting kit-8 (CCK-8) and flow cytometry were applied to analyze the cell viability and apoptosis. Co-immunoprecipitation experiment was utilized to assess the DJ-1-Cezanne interaction. The results showed that DJ-1 overexpression conferred apoptosis resistance and high proliferation on Ishikawa cells, while DJ-1 knockdown in Ishikawa cells produced the opposite results. These findings again suggested that DJ-1 inhibits the apoptosis and promotes the proliferation of Ishikawa cells. More crucially, further data showed that the noncanonical NF-κB activation was required for the regulation of Ishikawa cell proliferation and apoptosis by DJ-1. Meanwhile, it was found that noncanonical NF-κB pathway may be activated by DJ-1 interacting with and negatively regulating Cezanne in Ishikawa cells. CONCLUSIONS: Overall, this work revealed that DJ-1 associates with and negatively regulates Cezanne and consequently triggers the noncanonical NF-κB activation, thereby regulating Ishikawa cell proliferation and apoptosis.

Expression of DJ-1 in endometrial cancer: close correlation with clinicopathological features and apoptosis.

OBJECTIVES: DJ-1 was originally cloned as a putative oncogene capable of transforming NIH3T3 cells in cooperation with H-Ras or c-Myc, which has been implicated in the pathogenesis of some solid tumors. The aim of this study was to investigate the expression and clinical significance of DJ-1 in endometrial cancer and study its effect on cell proliferation and apoptosis in endometrial cancer Ishikawa cells. METHODS: Reverse transcription polymerase chain reaction and Western blotting were performed to determine the DJ-1 expression in 100 surgical specimens of endometrial cancer tissues, paired tumor-adjacent tissues, and 30 surgical specimens of normal endometrium tissues. The proliferation variety of endometrial cancer Ishikawa cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay after transfecting the interference plasmid pGPU6/GFP/neo-DJ-1-shRNA into Ishikawa cells. Real-time polymerase chain reaction and Western blotting were used to evaluate the effect of interference plasmid on target gene expression. Apoptosis rate was determined by flow cytometry. RESULTS: DJ-1 expression in endometrial cancer tissues was higher than in tumor-adjacent tissues and normal endometrial tissues. At the same time, it was associated with signs of cancer progression, including differentiation, myometrial invasion depth, and presence of lymph node metastasis. Knocking down DJ-1 promoted the apoptosis of Ishikawa cells. CONCLUSIONS: High DJ-1 expression seems to be negatively correlated with apoptosis. Meanwhile, it may be part of the mechanisms for the development, invasion, and metastasis in endometrial cancer.