USP13 serves as a tumor suppressor via the PTEN/AKT pathway in oral squamous cell carcinoma
Authors Qu Z, Zhang R, Su M, Liu W
Received 7 September 2018
Accepted for publication 17 January 2019
Published 31 October 2019 Volume 2019:11 Pages 9175—9183
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Kenan Onel
Zhi Qu1, Ran Zhang2, Meng Su2, Weixian Liu1
1Department of Oral and Maxillofacial Surgery, Shengjing Hospital, China Medical University, Shenyang, China; 2Department of Prosthodontics, Second Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
Correspondence: Weixian Liu
Department of Oral and Maxillofacial Surgery, Shengjing Hospital, China Medical University, No.36 Sanhao Street, Heping District, Shenyang, China
Background: Recent studies have shown that USP13 a deubiquitinase, serves as an important regulator of tumorigenesis. However, the biological role of USP13 in oral squamous cell carcinoma (OSCC) remains enigmatic.
Materials and methods: We examined USP13 expression in OSCC and adjacent normal tissues by immunohistochemical staining. The biological functions of USP13 in OSCC cells and the possible underlying mechanisms were investigated.
Results: In this study, we showed that USP13 expression was frequently reduced in human OSCC specimens and that the reduction was correlated with the clinical stage. Functional studies demonstrated that overexpression of USP13 suppressed OSCC cell proliferation, glucose uptake and lactate production in vitro and inhibited tumor growth in vivo. Furthermore, USP13 overexpression induced phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression and repressed the activation of AKT as well as the expression of the downstream effectors glucose transporter-1 (GLUT1) and hexokinase-2 (HK2). Overexpression of PTEN reversed the USP13-knockdown-induced glucose uptake, lactate production, AKT activation, and expression of GLUT1 and HK2.
Conclusion: Our findings suggest that USP13 serves as a tumor suppressor by regulating the PTEN/AKT signaling pathway in OSCC cells, improving our understanding of OSCC progression and providing a clue for the development of a novel cancer therapy.
Keywords: OSCC, USP13, PTEN, glycolysis
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