USP18‑deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal‑dependent manner

Pan,Aonan; Li,Yue; Guan,Jian; Zhang,Pengxia; Zhang,Chunbin; Han,Yupeng; Zhang,Tao; Cheng,Yao; Sun,Luo; Lu,Shizhen; Weng,Jinru; Ren,Qiaosheng; Fan,Shengjie; Wang,Weiqun; Wang,Jingtao

doi:10.3892/ol.2021.12682

USP18‑deficiency in cervical carcinoma is crucial for the malignant behavior of tumor cells in an ERK signal‑dependent manner

Authors:
- Aonan Pan
- Yue Li
- Jian Guan
- Pengxia Zhang
- Chunbin Zhang
- Yupeng Han
- Tao Zhang
- Yao Cheng
- Luo Sun
- Shizhen Lu
- Jinru Weng
- Qiaosheng Ren
- Shengjie Fan
- Weiqun Wang
- Jingtao Wang
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Affiliations: Department of Clinical Medicine, The Affiliated Second Hospital, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China, Departments of Immunology and Etiology, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China, Department of Maxillofacial Surgery, Stomatological College, Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China, Department of Biochemistry and Cell and Molecular Biology, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China, Department of Gastroenterology, The First Affiliated Hospital, Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China, Department of Clinical Laboratory, The First Affiliated Hospital, Jiamusi University, Jiamusi, Heilongjiang 154002, P.R. China, Department of Rehabilitation Medicine, Rehabilitation Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China, Department of Physiology, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China, Department of Human Anatomy, Basic Medical College, Jiamusi University, Jiamusi, Heilongjiang 154007, P.R. China
Published online on: March 29, 2021 https://doi.org/10.3892/ol.2021.12682
Article Number: 421
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ubiquitin‑specific peptidase (USP)18 belongs to the USP family, and is involved in cleaving and removing ubiquitin or ubiquitin‑like molecules from their target molecules. Recently, increasing evidence has suggested that USP18 is constitutively expressed in different types of human tumors, and ectopic expression or downregulation of USP18 expression may contribute to tumorigenesis. However, the role of USP18 in uterine cervical cancer (UCC) remains unclear. Thus, the present study aimed to investigate USP18 expression in a human tissue microarray constructed using UCC and non‑cancer cervical tissues, and to determine the potential role and molecular mechanism by which USP18 is implicated in the tumor biology of human UCC HeLa cells. Microarray analysis demonstrated that USP18 protein expression was downregulated in tumor tissues compared with in normal tissues. In addition, in vitro analysis revealed that USP18‑knockdown markedly promoted the proliferation, colony formation, migration and aggressiveness of HeLa cells. Mechanistic analysis demonstrated that USP18‑knockdown increased the levels of Bcl‑2, STAT3 and phosphorylated‑ERK in HeLa cells. Notably, USP18 silencing‑induced malignant phenotypes were interrupted following exogenous administration of the ERK1/2 inhibitor PD98059. Overall, the results of the present study suggested that USP18 may be a potent inhibitor involved in UCC tumor‑associated biological behaviors, which are associated with the ERK signaling pathway.

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