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Chen Huang, Zhaogeng Cai, Mingzhu Huang, Chaoming Mao, Qifa Zhang, Yi Lin, Xiaomei Zhang, Bi Tang, Yuqing Chen, Xiaojing Wang, Zhongqing Qian, Lei Ye, Yongde Peng, Huanbai Xu, miR-219–5p Modulates Cell Growth of Papillary Thyroid Carcinoma by Targeting Estrogen Receptor α, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 2, 1 February 2015, Pages E204–E213, https://doi.org/10.1210/jc.2014-2883
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Abstract
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. It has been demonstrated that micro-RNAs (miRNAs) are involved in the development of PTC. The miRNA-chromatin immunoprecipitation microarray assay revealed down-regulation of miR-219–5p; however, the effect of miR-219–5p on PTC cell growth remains unknown. This result implied the critical role of miR-219–5p in the development of PTC.
We investigated the association between miR-219–5p and PTC development. Expression of miR-219–5p was monitored in 30 PTC tissue specimens and compared with that in 30 normal thyroid tissue specimens. The effect of miR-219–5p on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanism was clarified by a reporter assay and rescue experiment.
The current study confirmed that miR-219–5p expression was inhibited in PTC tissue samples. There were statistically significant differences in the expression of miR-219–5p with regard to sex, tumor size, and lymph node metastasis in patients with PTC. Forced expression of miR-219–5p suppressed PTC cell proliferation and migration and promoted apoptosis. Further study showed that estrogen receptor (ER) α was the direct target of miR-219–5p and mediated the effect of miR-219–5p on PTC occurrence. Expression of miR-219–5p was inversely correlated with that of ERα. Importantly, ERα overexpression in PTC cells rescued the inhibitory effect of miR-219–5p on PTC cell proliferation and migration. Thus, our results indicated that miR-219–5p played a critical role in PTC growth by inhibiting ERα.
Our investigation identified miR-219–5p as a negative regulator of PTC development through targeting of ERα.