Li Minle, Zhao Xue, Yong Hongmei, Shang Bingqing, Lou Weihua, Wang You, Bai Jin
Cancer Institute, Xuzhou Medical University, Xuzhou, China.
Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Front Pharmacol. 2021 Dec 7;12:778698. doi: 10.3389/fphar.2021.778698. eCollection 2021.
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 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 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.
E3泛素连接酶F盒蛋白22(FBXO22)可靶向细胞活动的关键调节因子进行泛素化和降解,在肿瘤发生和转移中发挥重要作用。然而,FBXO22在上皮性卵巢癌中的功能尚未见报道。本研究旨在探讨FBXO22在上皮性卵巢癌进展和转移中的生物学功能及其具体调控机制。通过组织芯片免疫组化分析评估FBXO22在上皮性卵巢癌患者中的表达。采用CCK8检测上皮性卵巢癌细胞的增殖能力。通过伤口愈合实验、迁移和侵袭实验检测转移能力。利用蛋白质免疫印迹法验证FBXO22表达与丝裂原活化蛋白激酶相关蛋白之间的关系。通过电子显微镜、mRFP-GFP-LC3腺病毒、溶酶体示踪剂和蛋白质免疫印迹法检测自噬通量。在异种移植肿瘤模型和转移性小鼠模型中观察FBXO22对上皮性卵巢癌耐药性的影响。我们发现FBXO22在上皮性卵巢癌组织中的表达显著增加,且与临床病理因素密切相关。结果表明,FBXO22促进肿瘤生长和转移,同时抑制自噬通量。此外,我们确定FBXO22通过丝裂原活化蛋白激酶/细胞外信号调节激酶(MAPK/ERK)通路发挥这些功能。我们的研究首次报道了FBXO22在上皮性卵巢癌中的功能以及FBXO22与自噬之间的相关性,提示FBXO22可作为上皮性卵巢癌评估和治疗的新靶点。