Estrogen receptor β upregulated by lncRNA-H19 to promote cancer stem-like properties in papillary thyroid carcinoma

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Title: Estrogen receptor β upregulated by lncRNA-H19 to promote cancer stem-like properties in papillary thyroid carcinoma
Authors: Li, M
Chai, H-F
Peng, F
Meng, Y-T
Zhang, L-Z
Zhang, L
Zou, H
Liang, Q-L
Li, M-M
Mao, K-G
Sun, D-X
Tong, M-Y
Deng, Z-Q
Hou, Z-J
Zhao, Y
Li, J
Wang, X-C
Lv, S-S
Zhang, Q-Q
Yu, X
Lam, EW-F
Liu, Q
Cui, X-N
Xu, J
Item Type: Journal Article
Abstract: Estrogen receptor β (ERβ) plays critical roles in thyroid cancer progression. However, its role in thyroid cancer stem cell maintenance remains elusive. Here, we report that ERβ is overexpressed in papillary thyroid cancer stem cells (PTCSCs), whereas ablation of ERβ decreases stemness-related factors expression, diminishes ALDH+ cell populations, and suppresses sphere formation ability and tumor growth. Screening estrogen-responsive lncRNAs in PTC spheroid cells, we find that lncRNA-H19 is highly expressed in PTCSCs and PTC tissue specimens, which is correlated with poor overall survival. Mechanistically, estradiol (E2) significantly promotes H19 transcription via ERβ and elevates H19 expression. Silencing of H19 inhibits E2-induced sphere formation ability. Furthermore, H19 acting as a competitive endogenous RNA sequesters miRNA-3126-5p to reciprocally release ERβ expression. ERβ depletion reverses H19-induced stem-like properties upon E2 treatment. Appropriately, ERβ is upregulated in PTC tissue specimens. Notably, aspirin attenuates E2-induced cancer stem-like traits through decreasing both H19 and ERβ expression. Collectively, our findings reveal that ERβ-H19 positive feedback loop has a compelling role in PTCSC maintenance under E2 treatment and provides a potential therapeutic targeting strategy for PTC.
Issue Date: 2-Nov-2018
Date of Acceptance: 13-Sep-2018
ISSN: 2041-4889
Publisher: Nature Publishing Group
Journal / Book Title: Cell Death and Disease
Volume: 9
Copyright Statement: © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Sponsor/Funder: Cancer Research UK
Breast Cancer Now
Breast Cancer Now
Medical Research Council (MRC)
Funder's Grant Number: C37/A12011
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
Publication Status: Published
Article Number: ARTN 1120
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine

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