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

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.

Targeted inhibition of long non-coding RNA H19 blocks anaplastic thyroid carcinoma growth and metastasis

“…The mean H19 was increased in 19 frozen ATC tissues compared to the 19 patients with benign thyroid nodes who underwent thyroidectomy and/or or FNA tissues. Our study was agreed to Li's and Wächter's [24,25] but contrary to the Lan's [20]. The expression level and role of H19 in different tissues are different.…”

“…In PTC tissues, H19 was significantly higher than paired paracancerous tissue or normal tissues, and overexpression of H19 was correlated with higher tumor burden of PTCs [18]. Li et al also found that H19 is highly expressed in papillary thyroid cancer stem cells (PTCSCs) and PTC tissue specimens, which is correlated with poor overall survival [24]. However, Lan et al have reported that H19 is downregulated in PTC tissues and in PTC cell lines compared to controls, and decreased H19 expression was correlated with lymph node metastasis [20].…”

Hormone Replacement Therapy in Cancer Survivors – Review of the Literature

“…Estrogen receptor overexpression, however, has not only been found in the well-known estrogen dependent tumour types, such as breast, endometrial and ovarian cancer. Altered estrogen and / or progesterone receptor expression has been documented for example in thyroid cancer [12][13][14][15], Hodgkin's lymphoma [16][17][18], B-cell malignancies [19,20], brain tumours [21][22][23][24][25], prolactinoma [26,27], melanoma [28][29][30][31], lung cancer [32,33], colorectal cancer [34][35][36], gastric cancer [37] and liver cancer [38,39].…”

Exosomal lncRNA DOCK9-AS2 derived from cancer stem cell-like cells activated Wnt/β-catenin pathway to aggravate stemness, proliferation, migration, and invasion in papillary thyroid carcinoma

“…Former studies have illustrated that lncRNAs promoted PTC development and by regulating stemness 37 – 39 . CSCs are identified as crucial participants in tumor progression 16 , 17 .…”