It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Background: The deubiquitinating (DUB) enzyme ubiquitin-specific protease 18 (USP18), also known as UBP43, is an ubiquitin-specific protease and has been linked to several human malignancies. However, the underlying function of USP18 remains unclear in human cervical cancer. In the current research, we aimed to analyze the role of USP18 and its signaling pathway in cervical cancer.
Methods: Quantitative real time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to analyze USP18 levels in cervical cancer and adjacent-matched tissues. Moreover, RNA interference (RNAi) and lentiviral-mediated vector were performed to silence and overexpression of USP18 in cervical cancer cells. Further, Cell Counting Kit-8 (CCK-8) assay and Annexin V/PI staining were used to assess its biological function in cell proliferation and apoptosis respectively.
Results: Present findings demonstrated that USP18 was overexpressed in cervical cancer specimens and cell lines. Silencing of USP18 in cervical cancer cell lines, SiHa and Caski, inhibited cell proliferation, while induced apoptosis and promoted the expression of cleaved caspase-3. On the contrary, USP18 overexpression showed reversed effects in Hela cells. Gene Set Enrichment Analysis suggested that USP18 was enriched in PI3K/AKT signaling 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, the PI3K/AKT inhibitor LY294002 deeply abolished the effects of USP18 overexpression in cervical cancer cells.
Conclusions: The current study indicates USP18 was an oncogenic gene in cervical cancer. Our findings not only deepened the understanding the biological function of USP18 in the pathogenesis of cervical cancer but also provided novel insight for cervical cancer therapy. Trial registration: retrospectively registered.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer