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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
These findings support the idea that the regulation of miRNA expression synergizes with the traditional proliferation pathways in promoting cell growth.
Istituto di Endocrinologia ed Oncologia Sperimentale del CNR (Consiglio Nazionale delle Ricerche), Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facoltà di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli Federico II 80131 Naples, Italy.
Vincenza
V
Leone
Daniela
D
D'Angelo
Pierlorenzo
P
Pallante
Carlo Maria
CM
Croce
Alfredo
A
Fusco
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D005434:Flow Cytometry; D006042:Goiter / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D040081:Protein Array Analysis; D012313:RNA / Q000096:biosynthesis; D060888:Real-Time Polymerase Chain Reaction; D051900:Smad3 Protein / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*
D017362:Cyclic AMP Response Element-Binding Protein; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D051900:Smad3 Protein; D012313:RNA; D013972:Thyrotropin; D008156:Luciferases; D017868:Cyclic AMP-Dependent Protein Kinases