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 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.