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

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.

• Authors: Huan Zhao, Na Li, Yicun Pang, Jun Zhao, Xiaohua Wu
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 23 Issue 2 (02 2021) ISSN: 1791-3004 [Electronic] Greece
• PMID: 33313950 (Publication Type: Journal Article)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• GANT 61
• GLI1 protein, human
• GLI2 protein, human
• Hedgehog Proteins
• NANOG protein, human
• Nanog Homeobox Protein
• Nuclear Proteins
• Pyridines
• Pyrimidines
• Zinc Finger Protein GLI1
• Zinc Finger Protein Gli2
• Cisplatin

Topics

• ATP Binding Cassette Transporter, Subfamily B (metabolism)
• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Ovarian Epithelial (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm (drug effects, genetics)
• Female
• Hedgehog Proteins (metabolism, pharmacology)
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Nanog Homeobox Protein (genetics, metabolism)
• Nuclear Proteins (antagonists & inhibitors, biosynthesis, genetics)
• Ovarian Neoplasms (genetics, metabolism, pathology)
• Prognosis
• Pyridines (pharmacology)
• Pyrimidines (pharmacology)
• Signal Transduction (drug effects)
• Stem Cells (drug effects)
• Tumor Stem Cell Assay
• Young Adult
• Zinc Finger Protein GLI1 (antagonists & inhibitors, biosynthesis, genetics)
• Zinc Finger Protein Gli2 (antagonists & inhibitors, biosynthesis, genetics)