Gli affects the stemness and prognosis of epithelial ovarian cancer via homeobox protein NANOG

Zhao,Huan; Li,Na; Pang,Yicun; Zhao,Jun; Wu,Xiaohua

doi:10.3892/mmr.2020.11767

Gli affects the stemness and prognosis of epithelial ovarian cancer via homeobox protein NANOG

Authors:
- Huan Zhao
- Na Li
- Yicun Pang
- Jun Zhao
- Xiaohua Wu
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Affiliations: Department of Obstetrics and Gynecology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Oncology, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China, Teaching and Research Section of Obstetrics and Gynecology, Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China
Published online on: December 10, 2020 https://doi.org/10.3892/mmr.2020.11767
Article Number: 128
Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gli proteins are key transcription factors of the Hedgehog (HH) signaling pathway, which is associated with tumorigenesis and drug resistance. However, the role of the HH signaling pathway in epithelial ovarian cancer (EOC) remains unclear. Studies have demonstrated that in some tumors, homeobox protein NANOG (NANOG), a known stem cell marker, is a downstream effector of Gli. However, limited research has been conducted on the association between Gli and NANOG in EOC, particularly regarding their roles in the tumor stemness, such as tumor development, drug resistance and patient prognosis. Thus, the aim of the present study was to explore the aforementioned issues. In this study, Gli1, Gli2 and NANOG expression in EOC tissues was assessed using immunohistochemistry. Gene expression was also assessed using western blotting and reverse transcription‑quantitative PCR in SKOV3 cells treated with a Gli inhibitor and an HH agonist. Furthermore, cell proliferation, colony‑forming ability and cisplatin sensitivity were assessed using Cell Counting Kit‑8 and colony formation assays. The results showed that both Gli1 and NANOG were associated with cisplatin resistance and EOC disease stage, while the nuclear expression of Gli2 was significantly associated with cisplatin resistance. Together, the expression of Gli and NANOG predicted poor patient prognosis. Targeting Gli with GANT61 impeded tumor proliferation, reversed cisplatin resistance and colony formation, and reduced NANOG expression. To conclude, Gli and NANOG may be effective indicators of platinum resistance and prognosis in EOC. Targeting Gli may reduce the stemness of ovarian cancer cell, which may be achieved via indirect targeting of NANOG.

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