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10 May 2019 : Clinical Research  

Effect of Deubiquitinase Ovarian Tumor Domain-Containing Protein 5 (OTUD5) on Radiosensitivity of Cervical Cancer by Regulating the Ubiquitination of Akt and its Mechanism

Fengling Yin1B, Houguang He1C, Bei Zhang1D, Jianhua Zheng1E, Meng Wang1F, Meng Zhang1G, Hongxia Cui2A*

DOI: 10.12659/MSM.912904

Med Sci Monit 2019; 25:3469-3475

Abstract

BACKGROUND: The aim of this study was to investigate the role of deubiquitinase [ovarian tumor domain-containing protein 5 (OTUD5)] in regulating Akt ubiquitination and its effect on the radiosensitivity of cervical cancer.

MATERIAL AND METHODS: Cervical cancer C33A cells were cultured, and then 2 groups of cells (overexpressed cells and silenced cells) were established by overexpressing and silencing OTUD5 gene. Next, quantitative polymerase chain reaction (qPCR) was employed to detect the expression level of OTUD5 in cells in each group. Co-immunoprecipitation and Western blot (WB) analysis were applied to measure the expression level of phosphorylated protein kinase B (Akt) and the level of ubiquitination. The sensitivity of cells to radiotherapy in each group was detected via clone-forming efficiency assay. After that, Statistical Product and Service Solutions (SPSS) 17.0 software was employed for analyses. The t test, one-way analysis of variance (ANOVA), and p test were used. P<0.05 suggested that a difference was statistically significant.

RESULTS: The levels of phosphorylated Akt and ubiquitination in OTUD5-overexpressed C33A cells were lower than those in the OTUD5-silenced group and control group. The sensitivity of OTUD5-overexpressed C33A cells to radiotherapy was higher than that of the OTUD5-silenced group and control group.

CONCLUSIONS: OTUD5 affects the radiosensitivity of cervical cancer through the regulation of Akt deubiquitination.

Keywords: Proto-Oncogene Proteins c-akt, ubiquitination, Uterine Cervical Neoplasms, Apoptosis, Cell Proliferation, Deubiquitinating Enzymes, Endopeptidases, Gene Silencing, Ovarian Neoplasms, RNA, Small Interfering, Radiation Tolerance, Signal Transduction

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750