title: UBE2S associated with OSCC proliferation by promotion of P21 degradation via the ubiquitin-proteasome system.
abstract: Ubiquitin-conjugating enzyme E2S (UBE2S), a family of E2 protein in the ubiquitin-proteasome system, is highly expressed in several types of cancers; however, its roles in oral squamous cell carcinoma (OSCC) have not yet been well elucidated. The purpose of this study was to clarify the functional activities of UBE2S in OSCCs. We analyzed the expression levels of UBE2S in nine OSCC cell lines and primary OSCC tissues by quantitative reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry (IHC). The correlations between UBE2S expression and clinical classifications of OSCCs were analyzed using the IHC scoring system. We also used UBE2S knockdown OSCC cells for functional assays (proliferation assay, flow cytometry, and Western blotting). UBE2S was overexpressed in OSCCs in vitro and in vivo and was correlated significantly (P < 0.05) with the primary tumoral size. The cellular growth was decreased and the cell-cycle was arrested in the G2/M phase in the UBE2S knockdown (shUBE2S) cells. The expression level of P21, a target of the ubiquitin-proteasome system, was increased in the shUBE2S cells because of lower anaphase activity that promotes complex subunit 3 (APC3), an E3 ubiquitin ligase, compared with shMock cells. These findings might promote the understanding of the relationship between UBE2S overexpression and oral cancer proliferation, indicating that UBE2S would be a potential biomarker of and therapeutic target in OSCCs.
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Yoshimura
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan. Electronic address: kasamatsua@faculty.chiba-u.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kasamatsu
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Nakashima
authors.affiliation: Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Iyoda
authors.affiliation: Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kasama
authors.affiliation: Division of Oral Surgery, Chiba Rosai Hospital, Chiba, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Takahara
authors.affiliation: Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Endo-Sakamoto
authors.affiliation: Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiiba
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Tanzawa
authors.affiliation: Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba, Japan; Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba, Japan. Electronic address: uzawak@faculty.chiba-u.jp.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Uzawa
mesh_terms: D000368:Aged; D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*
chemical_list: D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577366:CDC27 protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D025801:Ubiquitin; C544962:Ube2S protein, human; D044763:Ubiquitin-Conjugating Enzymes; D046988:Proteasome Endopeptidase Complex
keywords: APC/C; Cell cycle; G2/M arrest; Oral squamous cell carcinoma; P21; Ubiquitin-proteasome system