Abstract
E3 ubiquitin ligase F-box only protein 22 (FBXO22), which targets the key regulators of cellular activities for ubiquitylation and degradation, plays an important role in tumorigenesis and metastasis. However, the function of FBXO22 in epithelial ovarian cancers has not been reported. This study aims to explore the biological function of FBXO22 in epithelial ovarian cancers progression and metastasis and its specific regulation mechanism. Immunohistochemistry analysis of tissue microarray was performed to evaluate the expression of FBXO22 in epithelial ovarian cancers patients. The proliferative ability of epithelial ovarian cancers cells was examined by the CCK8. The metastasis ability was detected by the wound healing assay, migration and invasion assays. Western blot was used to verify the relationship between FBXO22 expression and mitogen-activated protein kinase related proteins. Autophagic flux was detected by electron microscopy, mRFP-GFP-LC3 adenovirus, lysosomal tracker and western blot. For in vivo experiments, the effect of FBXO22 on epithelial ovarian cancers resistance was observed in a xenograft tumor model and a metastatic mice model. We found that FBXO22 expression was significantly increased in epithelial ovarian cancers tissues and was closely correlated with clinical pathological factors. As a result, we found that FBXO22 promoted the growth and metastasis, as well as inhibited the autophagy flux. In addition, we identified that FBXO22 performed these functions via the MAPK/ERK pathway. Our results first reported the function of FBXO22 in epithelial ovarian cancer and the correlation between FBXO22 and autophagy, suggesting FBXO22 as a novel target of epithelial ovarian cancers assessment and treatment.
Highlights
Ovarian cancer is the seventh most common cancer among women, and the age-standardized rates in developed and developing countries are approximately 9.4 and 5.0 per 100,000 people, respectively (Siegel et al, 2016; Reid et al, 2017)
To evaluate whether the F-box only protein 22 (FBXO22) protein expression is related to epithelial ovarian cancers (EOCs), we performed immunohistochemistry experiments across an entire tissue microarray (TMA) containing 251 EOCs tissues and 10 matched
The results shown that the rate of transformation from LC3 I to LC3 II increased and the substrate P62 decreased after FBXO22 interference, indicating that autophagy was enhanced (Figure 7A)
Summary
Ovarian cancer is the seventh most common cancer among women, and the age-standardized rates in developed and developing countries are approximately 9.4 and 5.0 per 100,000 people, respectively (Siegel et al, 2016; Reid et al, 2017). Cytoreductive surgery is clinically adopted, along with chemotherapy using cisplatin and paclitaxel, but the multidrug resistance of ovarian cancer cells has severely reduced the long-term efficacy of these treatments; the 5-year survival rate is only 30% (Coleman et al, 2013). Issues concerning the in-depth exploration of the mechanism of the occurrence, development, invasion, and metastasis of ovarian cancer cells and in the search for effective targeted treatment approaches need to be resolved urgently
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