Exosome Component 4 Promotes Epithelial Ovarian Cancer Cell Proliferation, Migration, and Invasion via the Wnt Pathway

Abstract

BackgroundOf gynecologic malignancies, ovarian cancer is the leading cause of death, mainly due to the lack of sensitive tumor markers, which means it almost always presents at an advanced stage. Exosome Component 4 (EXOSC4) is involved in RNA degradation, but its role in epithelial ovarian cancer (EOC) is unclear.MethodsThe expression levels of EXOSC4 in EOC and normal ovarian tissue specimens were determined by immunohistochemical staining. The overall survival (OS) and progression-free survival (PFS) of patients with EOC were evaluated after patients were classified into high and low EXOSC4 expression groups, and the Cox regression model was established to identify independent predictors of patient prognosis. The effects of EXOSC4 on proliferation, colony formation, migration, and invasion were examined in the SKOV-3 and HO8910 cell lines by lentivirus-mediated shRNA knockdown. Flow cytometry was used to detect cell cycle changes. The mRNA levels of cyclin D1, CDK4, and c-myc were detected by RT-PCR. The protein expression levels of β-catenin, cyclin D1, CDK4, c-myc, vimentin, N-cadherin, and E-cadherin were assessed by western blot. Wnt/β-catenin activation was measured by TCF/LEF reporter assay.ResultsEXOSC4 was significantly elevated in EOC tissues and cell lines. High EXOSC4 expression was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and pathological grade, and identified as an independent predictor of shorter OS and PFS. EXOSC4 knockdown suppressed proliferation, migration, and invasion in EOC cell lines. Cells were arrested at G0/G1 phase after EXOSC4 knockdown. The mRNA levels of cyclin D1, CDK4, and c-myc were decreased. β-catenin, cyclin D1, CDK4, c-myc, vimentin, and N-cadherin protein expression levels were reduced, while those of E-cadherin was increased. Wnt/β-catenin activity was suppressed after the EXOSC4 knockdown.ConclusionsEXOSC4 is involved in EOC. Knockdown of EXOSC4 can inhibit the proliferation, migration, and invasion ability of EOC by suppressing the Wnt pathway. EXOSC4 is expected to be a novel biomarker and molecular target in EOC.

Comprehensive Analysis of Purine-Metabolism-Related Gene Signature for Predicting Ovarian Cancer Prognosis, Immune Landscape, and Potential Treatment Options

“…Similarly, low expression of PDIA4 has been reported to be associated with shorter survival in ovarian tumors, especially in drugresistant tissues [29,30]. Another interesting point is that high EXOSC4 expression promotes malignant features of OC via the Wnt pathway and correlates with higher FIGO stage and pathological grade, although it is a protective factor in our signature [31]. Although the relationship between other genes and OC has not been adequately studied, they have been reported to play a role in other cancers.…”

The current trend of exosome in epithelial ovarian cancer studies: A bibliometric review

“…Only articles published in English were included. After the exclusion of duplicate, irrelevant journal articles and non-journal articles, 39 articles on exosome and EOC were selected for bibliometric analysis; 36 of which were original articles ( Zhang et al, 2016a ; Meng et al, 2016b ; Zhang et al, 2016b ; Labani-Motlagh et al, 2016 ; Ying et al, 2016 ; Chen et al, 2017 ; Hu et al, 2017 ; Li et al, 2017 ; Wu et al, 2017 ; Chen et al, 2018 ; Qiu et al, 2018 ; Zhang et al, 2018 ; Zhou et al, 2018 ; Zhang et al, 2019a ; Keserű et al, 2019 ; Tang et al, 2019 ; Zhu et al, 2019 ; Cheng et al, 2020 ; Li et al, 2020 ; Lu et al, 2020 ; Luo and Gui, 2020 ; Maeda et al, 2020 ; Masoumi-Dehghi et al, 2020 ; Alharbi et al, 2021 ; Xiong et al, 2021a ; Cai et al, 2021 ; Gao et al, 2021 ; Li et al, 2021 ; Liu et al, 2021 ; Ma et al, 2021 ; Zhu et al, 2022a ; Chen et al, 2022 ; Jeon et al, 2022 ; Lai et al, 2022 ; Yang et al, 2022 ), and the rest of them were review articles ( Li and Wang, 2017 ; Lucidi et al, 2020 ; Shiao et al, 2021 ). The first English article is “Characterization of exosomes derived from ovarian cancer cells and normal ovarian epithelial cells by nanoparticle tracking analysis” in 2015 ( Zhang et al, 2016a ).…”

Identification of novel a chromatin regulator signature predicting overall survival for breast cancer

“…The alteration of EXOSC4 was associated with the OS and PFS pancreatic cancer patients [20]. Downregulation of EXOSC4 can inhibit cancer cell migration and invasion [21,22]. Taniue et al also showed that EXOSC4 knockdown led to the reduction in the viability of pancreatic and colorectal tumor cells [20].…”