USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway
Abstract 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...
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doaj-625bb50ea17841cc84ed43212230195e2020-11-25T02:54:21ZengBMCBMC Cancer1471-24072020-08-012011910.1186/s12885-020-07241-1USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathwayWenjing Diao0Qisang Guo1Caiying Zhu2Yu Song3Hua Feng4Yuankui Cao5Ming Du6Huifen Chen7Medical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityMedical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityMedical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityMedical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityMedical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityMedical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityMedical Center of Cervical Diseases, Obstetrics and Gynecology Hospital, Fudan UniversityDepartment of Laboratory Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12885-020-07241-1Cervical cancerUSP18AKTProliferationApoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wenjing Diao Qisang Guo Caiying Zhu Yu Song Hua Feng Yuankui Cao Ming Du Huifen Chen |
spellingShingle |
Wenjing Diao Qisang Guo Caiying Zhu Yu Song Hua Feng Yuankui Cao Ming Du Huifen Chen USP18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating AKT signaling pathway BMC Cancer Cervical cancer USP18 AKT Proliferation Apoptosis |
author_facet |
Wenjing Diao Qisang Guo Caiying Zhu Yu Song Hua Feng Yuankui Cao Ming Du Huifen Chen |
author_sort |
Wenjing Diao |
title |
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_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_sort |
usp18 promotes cell proliferation and suppressed apoptosis in cervical cancer cells via activating akt signaling pathway |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2020-08-01 |
description |
Abstract 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. |
topic |
Cervical cancer USP18 AKT Proliferation Apoptosis |
url |
http://link.springer.com/article/10.1186/s12885-020-07241-1 |
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