Ling, K, Jiang, L, Liang, S, Kwong, J ORCID: https://orcid.org/0000-0002-3380-6882, Yang, L, Li, Y, Ping, Y, Deng, Q and Liang, Z (2018) Nanog interaction with the androgen receptor signaling axis induce ovarian cancer stem cell regulation: studies based on the CRISPR/Cas9 system. Journal of Ovarian Research, 11 (1). 36 - ?.

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Abstract

BACKGROUND: Ovarian cancer stem cells (OCSCs) contribute to the poor prognosis of ovarian cancer. Involvement of the androgen receptor (AR) in the malignant behaviors of other tumors has been reported. However, whether AR associates with Nanog (a stem cell marker) and participates in OCSC functions remain unclear. In this study, we investigated the interaction of Nanog with AR and examined whether this interaction induced stem-like properties in ovarian cancer cells. METHODS: AR and Nanog expression in ovarian tumors was evaluated. Using the CRISPR/Cas9 system, we constructed a Nanog green fluorescent protein (GFP) marker cell model to investigate the expression and co-localization of Nanog and AR. Then, we examined the effect of androgen on the Nanog promoter in ovarian cancer cell lines (A2780 and SKOV3). After androgen or anti-androgen treatment, cell proliferation, migration, sphere formation, colony formation and tumorigenesis were assessed in vitro and in vivo. RESULTS: Both AR and Nanog expression were obviously high in ovarian tumors. Our results showed that Nanog expression was correlated with AR expression. The androgen 5α-dihydrotestosterone (DHT) activated Nanog promoter transcription. Meanwhile, Nanog GFP-positive cells treated with DHT exhibited higher levels of proliferation, migration, sphere formation and colony formation. We also observed that the tumorigenesis of Nanog GFP-positive cells was significantly higher than that of the GFP-negative cells. Xenografts of Nanog GFP-positive cells showed significant differences when treated with androgen or anti-androgen drugs in vivo. CONCLUSIONS: The interaction of Nanog with the AR signaling axis might induce or contribute to OCSC regulation. In addition, androgen might promote stemness characteristics in ovarian cancer cells by activating the Nanog promoter. This finding merits further study because it may provide a new understanding of OCSC regulation from a hormone perspective and lead to the reevaluation of stem cell therapy for ovarian cancer.

Item Type: Article
Additional Information: Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords: Androgens (D000728), Animals (D000818), CRISPR-Cas Systems (D064113), Carcinogenesis (D063646), Cell Line, Tumor (D045744), Cell Movement (D002465), Cell Proliferation (D049109), Female (D005260), Gene Expression Regulation, Neoplastic (D015972), Humans (D006801), Mice (D051379), Nanog Homeobox Protein (D000071317), Neoplastic Stem Cells (D014411), Ovarian Neoplasms (D010051), Ovary (D010053), Promoter Regions, Genetic (D011401), Receptors, Androgen (D011944), Signal Transduction (D015398), Xenograft Model Antitumor Assays (D023041), Androgen receptor signaling axis, Nanog, Ovarian cancer, Stemness properties
Subjects: R Medicine > R Medicine (General)
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 11 Mar 2020 09:56
Last Modified: 11 Mar 2020 09:56
URI: http://eprints.keele.ac.uk/id/eprint/7789

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