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

ABSTRACT: Estrogen receptor ? (ER?) plays critical roles in thyroid cancer progression. However, its role in thyroid cancer stem cell maintenance remains elusive. Here, we report that ER? is overexpressed in papillary thyroid cancer stem cells (PTCSCs), whereas ablation of ER? 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 ER? 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 ER? expression. ER? depletion reverses H19-induced stem-like properties upon E2 treatment. Appropriately, ER? is upregulated in PTC tissue specimens. Notably, aspirin attenuates E2-induced cancer stem-like traits through decreasing both H19 and ER? expression. Collectively, our findings reveal that ER?-H19 positive feedback loop has a compelling role in PTCSC maintenance under E2 treatment and provides a potential therapeutic targeting strategy for PTC.


PROVIDER: S-EPMC6214949 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

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