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Updated: Mar 26, 2026

In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting CCDC6 Gene
Vincenza Leone1, Concetta Langella1, Francesco Esposito1
1Istituto di Endocrinologia ed Oncologia Sperimentale-CNR, Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Scuola di Medicina e Chirurgia di Napoli, Università degli Studi di Napoli 'Federico II', Naples, Italy.
Abstract:
We have previously studied the function of microRNAs (miRNAs) in thyroid cells using the differentiated rat thyroid PC Cl 3 cells that need thyrotropin (TSH) for their growth. The miRNA expression profile examination allowed the detection of a set of miRNAs downregulated and upregulated by TSH. Here, we first demonstrated that upregulation of miR-130b-3p occurs through a protein kinase A-cAMP-responsive element binding protein (CREB)-dependent mechanism. Then, we analyzed its expression in human thyroid follicular adenomas, where a constitutive CREB activation is frequently present. miR-130b-3p results in upregulation with a high fold-change in most thyroid follicular adenomas. Then, we identified CCDC6, coding for a protein that interacts with CREB1 leading to the transcriptional repression of CREB1 target genes, as a target of this miRNA. The targeting of CCDC6 by miR-130b-3p likely accounts for the mechanism by which its upregulation contributes to the development of thyroid adenomas increasing CREB1 activity.
Insights
Thyroid-stimulating hormone (TSH) upregulates miR-130b-3p via a CREB-dependent pathway. This microRNA targets CCDC6, promoting thyroid adenoma development by enhancing CREB1 activity.
Area of Science:
- Endocrinology
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) play crucial roles in cellular functions, including thyroid cell growth.
- Thyroid-stimulating hormone (TSH) influences miRNA expression in thyroid cells.
- Thyroid follicular adenomas are common endocrine tumors often associated with altered signaling pathways.
Purpose of the Study:
- To elucidate the regulatory mechanism of miR-130b-3p upregulation by TSH.
- To investigate the role of miR-130b-3p in human thyroid follicular adenomas.
- To identify the downstream targets of miR-130b-3p involved in thyroid tumorigenesis.
Main Methods:
- Analysis of miRNA expression profiles in response to TSH stimulation.
- Investigation of the protein kinase A-cAMP-responsive element binding protein (CREB) pathway.
- Expression analysis of miR-130b-3p in human thyroid follicular adenomas.
- Identification of miRNA targets using bioinformatics and experimental validation.
Main Results:
- TSH upregulates miR-130b-3p through a protein kinase A-cAMP-responsive element binding protein (CREB)-dependent mechanism.
- miR-130b-3p is significantly upregulated in most thyroid follicular adenomas.
- CCDC6, a repressor of CREB1 target genes, was identified as a direct target of miR-130b-3p.
- Targeting CCDC6 by miR-130b-3p leads to increased CREB1 activity.
Conclusions:
- miR-130b-3p upregulation, mediated by TSH and CREB, contributes to thyroid adenoma development.
- The miR-130b-3p/CCDC6 axis represents a novel mechanism in thyroid tumorigenesis.
- Targeting this pathway may offer therapeutic strategies for thyroid follicular adenomas.
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