Thyrotropin regulates thyroid cell proliferation by up-regulating miR-23b and miR-29b that target SMAD3.

Abstract

MicroRNA (miRNA or miR) have emerged as an important class of short endogenous RNA that act as post-transcriptional regulators of gene expression and have a critical role in cell proliferation and differentiation. The aim of this study was to elucidate the role of miRNA in the proliferation of differentiated thyroid cells that require TSH for their growth. To elucidate the role of miRNA in thyroid cell proliferation, we have analyzed the miRNA expression profile of PC Cl 3 cells before and after the stimulation by TSH. We report the identification of two specific miRNA (miR-23b and miR-29b) whose up-regulation by TSH is required for thyroid cell growth. We identified mothers against decapentaplegic homolog 3 (Smad3), a member of the TGF-β pathway that has an inhibitor role in thyroid follicular cell proliferation as a target of miR-23b and miR-29b. Functional studies demonstrated that the overexpression of miR-23b and miR-29b promotes thyroid cell growth. Interestingly, an increased expression of both these miRNA was also detected in experimental and human goiters. These findings support the idea that the regulation of miRNA expression synergizes with the traditional proliferation pathways in promoting cell growth.