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USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway
BACKGROUND: The deubiquitinating (DUB) enzyme ubiquitin-specific protease 18 (USP18), also known as UBP43, is an ubiquitin-specific protease linked to several human malignancies. However, USP18’s underlying function in human cervical cancer remains unclear. In the current study, we aimed to analyse...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414560/ https://www.ncbi.nlm.nih.gov/pubmed/32770981 http://dx.doi.org/10.1186/s12885-020-07241-1 |
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author | Diao, Wenjing Guo, Qisang Zhu, Caiying Song, Yu Feng, Hua Cao, Yuankui Du, Ming Chen, Huifen |
author_facet | Diao, Wenjing Guo, Qisang Zhu, Caiying Song, Yu Feng, Hua Cao, Yuankui Du, Ming Chen, Huifen |
author_sort | Diao, Wenjing |
collection | PubMed |
description | BACKGROUND: The deubiquitinating (DUB) enzyme ubiquitin-specific protease 18 (USP18), also known as UBP43, is an ubiquitin-specific protease linked to several human malignancies. However, USP18’s underlying function in human cervical cancer remains unclear. In the current study, we aimed to analyse the role of USP18 and its signalling pathways in cervical cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to analyse USP18 levels in cervical cancer and matched to adjacent normal tissues. Moreover, RNA interference (RNAi) and lentiviral-mediated vector transfections were performed to silence and overexpress USP18, respectively, in cervical cancer cells. Further, Cell Counting Kit-8 (CCK-8) and Annexin V/PI staining assays were used to assess its biological function in cell proliferation and apoptosis, respectively. A xenograft model was used to examine USP18’s function in vivo. RESULTS: The present findings demonstrated that USP18 was overexpressed in cervical cancer specimens and cell lines. Silencing USP18 in SiHa and Caski cervical cancer cell lines inhibited cell proliferation, induced apoptosis, and promoted cleaved caspase-3 expression. In contrast, USP18 overexpression showed the opposite effects in human HcerEpic cells. A Gene Set Enrichment Analysis revealed that USP18 was enriched in the PI3K/AKT signalling pathway in cervical cancer. Hence, the PI3K/AKT inhibitor LY294002 was used to determine the relationship between USP18 and AKT in cervical cancer cells. Importantly, LY294002 significantly abolished the effects of USP18 overexpression in cervical cancer cells. In vivo, USP18 silencing inhibited human cervical cancer cells’ tumorigenicity. CONCLUSIONS: The current study indicates that USP18 is an oncogenic gene in cervical cancer. Our findings not only deepened the understanding of USP18’s biological function in cervical cancer pathogenesis, but we also provided novel insight for cervical cancer therapy. TRIAL REGISTRATION: Retrospectively registered. |
format | Online Article Text |
id | pubmed-7414560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-74145602020-08-10 USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway Diao, Wenjing Guo, Qisang Zhu, Caiying Song, Yu Feng, Hua Cao, Yuankui Du, Ming Chen, Huifen BMC Cancer Research Article BACKGROUND: The deubiquitinating (DUB) enzyme ubiquitin-specific protease 18 (USP18), also known as UBP43, is an ubiquitin-specific protease linked to several human malignancies. However, USP18’s underlying function in human cervical cancer remains unclear. In the current study, we aimed to analyse the role of USP18 and its signalling pathways in cervical cancer. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to analyse USP18 levels in cervical cancer and matched to adjacent normal tissues. Moreover, RNA interference (RNAi) and lentiviral-mediated vector transfections were performed to silence and overexpress USP18, respectively, in cervical cancer cells. Further, Cell Counting Kit-8 (CCK-8) and Annexin V/PI staining assays were used to assess its biological function in cell proliferation and apoptosis, respectively. A xenograft model was used to examine USP18’s function in vivo. RESULTS: The present findings demonstrated that USP18 was overexpressed in cervical cancer specimens and cell lines. Silencing USP18 in SiHa and Caski cervical cancer cell lines inhibited cell proliferation, induced apoptosis, and promoted cleaved caspase-3 expression. In contrast, USP18 overexpression showed the opposite effects in human HcerEpic cells. A Gene Set Enrichment Analysis revealed that USP18 was enriched in the PI3K/AKT signalling pathway in cervical cancer. Hence, the PI3K/AKT inhibitor LY294002 was used to determine the relationship between USP18 and AKT in cervical cancer cells. Importantly, LY294002 significantly abolished the effects of USP18 overexpression in cervical cancer cells. In vivo, USP18 silencing inhibited human cervical cancer cells’ tumorigenicity. CONCLUSIONS: The current study indicates that USP18 is an oncogenic gene in cervical cancer. Our findings not only deepened the understanding of USP18’s biological function in cervical cancer pathogenesis, but we also provided novel insight for cervical cancer therapy. TRIAL REGISTRATION: Retrospectively registered. BioMed Central 2020-08-08 /pmc/articles/PMC7414560/ /pubmed/32770981 http://dx.doi.org/10.1186/s12885-020-07241-1 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Article Diao, Wenjing Guo, Qisang Zhu, Caiying Song, Yu Feng, Hua Cao, Yuankui Du, Ming Chen, Huifen USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway |
title | USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway |
title_full | USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway |
title_fullStr | USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway |
title_full_unstemmed | USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway |
title_short | USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway |
title_sort | usp18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating akt signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414560/ https://www.ncbi.nlm.nih.gov/pubmed/32770981 http://dx.doi.org/10.1186/s12885-020-07241-1 |
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