Role of <i>Dicer1</i> in thyroid cell proliferation and differentiation

<p><i>DICER1</i> plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and <i>DICER1</i> dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within <i>DICER1</i> gene of an unknown function. Herein, we show that <i>DICER1</i> is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, <i>DICER1</i> is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that <i>DICER1</i> overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of <i>DICER1</i> gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates <i>DICER1</i> protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, <i>DICER1</i> protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while <i>DICER1</i> gene mutation (c.5438A>G; E1813G) compromises the <i>DICER1</i> wild-type-mediated microRNA processing and cell proliferation.</p>