title: Ubiquitin specific protease 22 promotes cell proliferation and tumor growth of epithelial ovarian cancer through synergy with transforming growth factor β1.
abstract: Ubiquitin specific protease 22 (USP22) is an oncogene that is upregulated in many cancer types, and aberrant expression of USP22 correlates with clinical outcome. However, its potential functional impact in epithelial ovarian cancer (EOC) has not been determined. Here, we report that USP22 was upregulated in EOC specimens and EOC cell lines with important functional consequences. A high level of USP22 in EOC tissues was associated with advanced clinical FIGO stage, lymph node metastasis and worse prognosis. Patients with higher USP22 expression had shorter relapse-free and overall survival. Depletion of USP22 suppressed cell proliferation in vitro and tumor growth in vivo. We found that inhibition of USP22 suppressed cell proliferation by inducing G1 phase cell cycle arrest through synergy with oncogenic transforming growth factor-β1 (TGFB1). Our results indicate that USP22 functions as an oncogene in EOC, and thus USP22 may serve as a potential therapeutic target for individualized EOC treatment.
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Shunshuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Chang
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xinghan
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction; D013869:Thiolester Hydrolases / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D047368:Tumor Burden; D043222:Ubiquitin Thiolesterase
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D013869:Thiolester Hydrolases; D043222:Ubiquitin Thiolesterase; C527170:Usp22 protein, human