The microRNA-Processing Enzyme Dicer Is Essential for Thyroid Function

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.

• Publication year

  2011

• Venue

  PLoS ONE

• Publication date

  2011-11-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0027648PMID 22132122PMCID 3221669
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Upregulation of miR-21 by Ras in vivo and its role in tumor growth

  2011cited by this paper
• A MicroRNA targeting dicer for metastasis control.

  2010cited by this paper
• Downregulation of microRNAs directs the EMT and invasive potential of anaplastic thyroid carcinomas

  2010cited by this paper
• Morphogenesis of the thyroid gland.

  2010cited by this paper
• Dicer Ablation Impairs Prostate Stem Cell Activity and Causes Prostate Atrophy

  2010cited by this paper
• Dicer is required for proper liver zonation

  2009cited by this paper
• Dicer Is Required for Maintaining Adult Pancreas

  2009cited by this paper
• An autoregulatory loop mediated by miR-21 and PDCD4 controls the AP-1 activity in RAS transformation

  2009cited by this paper
• Biogenesis of small RNAs in animals

  2009cited by this paper
• Different timings of dicer deletion affect neurogenesis and gliogenesis in the developing mouse central nervous system

  2009cited by this paper
• Podocyte-specific loss of functional microRNAs leads to rapid glomerular and tubular injury.

  2008cited by this paper
• Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure

  2008cited by this paper
• Conditional Loss of Dicer Disrupts Cellular and Tissue Morphogenesis in the Cortex and Hippocampus

  2008cited by this paper
• Podocyte-specific deletion of dicer alters cytoskeletal dynamics and causes glomerular disease.

  2008cited by this paper
• Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?

  2008cited by this paper
• Podocyte-selective deletion of dicer induces proteinuria and glomerulosclerosis.

  2008cited by this paper
• A mammalian microRNA expression atlas based on small RNA library sequencing.

  2007cited by this paper
• Conditional inactivation of the E-cadherin gene in thyroid follicular cells affects gland development but does not impair junction formation.

  2007cited by this paper
• Dicer function is essential for lung epithelium morphogenesis

  2006cited by this paper
• The diverse functions of microRNAs in animal development and disease.

  2006cited by this paper
• Characterization of Dicer-deficient murine embryonic stem cells.

  2005cited by this paper
• A mouse model demonstrates a multigenic origin of congenital hypothyroidism.

  2005cited by this paper
• The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb.

  2005cited by this paper
• Human RISC couples microRNA biogenesis and posttranscriptional gene silencing.

  2005cited by this paper
• Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets.

  2005cited by this paper
• Intensified Cloning Efforts Have Revealed Numer

  2004cited by this paper
• Tissue‐specific expression of cre recombinase from the Pax8 locus

  2004cited by this paper
• MicroRNAs: small RNAs with a big role in gene regulation

  2004cited by this paper
• Thyroid development and its disorders: genetics and molecular mechanisms.

  2004cited by this paper
• Dicer is essential for mouse development

  2003cited by this paper
• The Paired Domain-containing Factor Pax8 and the Homeodomain-containing Factor TTF-1 Directly Interact and Synergistically Activate Transcription*

  2003cited by this paper
• Dicer is essential for mouse development

  2003cited by this paper
• Multiple Ras Downstream Pathways Mediate Functional Repression of the Homeobox Gene Product TTF-1

  2000cited by this paper
• The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain.

  1991cited by this paper

• Dicer1 Depletion Leads to DNA Damage Accumulation and Cell Death in a RET/PTC3 Papillary Thyroid Cancer Mouse Model, Thereby Inhibiting Tumor Progression

  2025cites this paper
• Thyroblastoma as a manifestation of DICER1 syndrome with confirmed germline mutation and comprehensive literature review

  2025cites this paper
• Distinctive role of DICER1 mutations in distant metastatic thyroid cancer.

  2024cites this paper
• Somatic DICER1-Mutant Benign Thyroid Nodules in Adults: A Group of Follicular Nodular Disease With Continuous Growth.

  2024cites this paper
• Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics

  2024cites this paper
• DICER1 RNase IIIb domain mutations trigger widespread miRNA dysregulation and MAPK activation in pediatric thyroid cancer

  2023cites this paper
• An institutional experience with DICER1 mutated thyroid nodules-evaluating the cytomorphology and molecular phenotype.

  2022cites this paper
• MiRNA Deregulation Distinguishes Anaplastic Thyroid Carcinoma (ATC) and Supports Upregulation of Oncogene Expression

  2021cites this paper
• Functional conservation in genes and pathways linking ageing and immunity

  2021cites this paper
• Recurrent DICER1 Hotspot Mutations in Malignant Thyroid Gland Teratomas

  2020cites this paper
• Transcriptomic profiling of long- and short-lived mutant mice implicates mitochondrial metabolism in ageing and shows signatures of normal ageing in progeroid mice

  2020cites this paper
• Thyroid hormone, gene expression, and Central Nervous System: Where we are.

  2020cites this paper
• The critical impacts of small RNA biogenesis proteins on aging, longevity and age-related diseases.

  2020cites this paper
• Thyroid Follicular Cell Loss of Differentiation Induced by MicroRNA miR-17-92 Cluster Is Attenuated by CRISPR/Cas9n Gene Silencing in Anaplastic Thyroid Cancer

  2020cites this paper
• Genetic Mutations and Variants in the Susceptibility of Familial Non-Medullary Thyroid Cancer

  2020cites this paper
• A Positive Feedback Loop Between DICER1 and Differentiation Transcription Factors Is Important for Thyroid Tumorigenesis

  2020influential citation
• Follicular cell lineage in persistent ultimobranchial remnants of mammals

  2019cites this paper
• Impaired microRNA processing by DICER1 downregulation endows thyroid cancer with increased aggressiveness

  2019cites this paper
• Genetic analysis of a hereditary medullary thyroid carcinoma case with normal preoperative serum calcitonin levels.

  2019cites this paper
• Interplay of TGFβ signaling and microRNA in thyroid cell loss of differentiation and cancer progression

  2019cites this paper
• Constitutive Dicer1 phosphorylation accelerates metabolism and aging in vivo

  2018cites this paper
• Unraveling the Mechanistic Complexity of the Glomerulocystic Phenotype in Dicer Conditional KO Mice by 2D Gel Electrophoresis Coupled Mass Spectrometry

  2018influential citation
• The role of microRNAs in different types of thyroid carcinoma: a comprehensive analysis to find new miRNA supplementary therapies

  2018cites this paper
• Ionizing Radiation Deregulates the MicroRNA Expression Profile in Differentiated Thyroid Cells

  2018cites this paper
• Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion.

  2018cites this paper
• Genetically modified mouse models to investigate thyroid development, function and growth.

  2018cites this paper
• Should a Young Patient in Whom a Multinodular Goiter Develops Be Assessed for DICER1 Mutations?

  2018cites this paper
• Dicer expression is impaired in diabetic cutaneous wound healing

  2018cites this paper
• PHOSPHORYLATION IMPAIRS DICER1 FUNCTION TO ACCELERATE AGING AND TUMORIGENESIS IN VIVO

  2018cites this paper
• Impaired miRNA processing by DICER1 downregulation endows thyroid cancer with increased aggressiveness

  2018cites this paper
• MicroRNA-mediated dynamic control of mucosal immunity.

  2017cites this paper
• The Emerging Role of Epigenetics in Autoimmune Thyroid Diseases

  2017cites this paper
• MicroRNA-363-3p inhibits papillary thyroid carcinoma progression by targeting PIK3CA.

  2017cites this paper
• Role of Dicer1 in thyroid cell proliferation and differentiation

  2017cites this paper
• Viruses and miRNAs: More Friends than Foes

  2017cites this paper
• The co-occurrence of an ovarian Sertoli-Leydig cell tumor with a thyroid carcinoma is highly suggestive of a DICER1 syndrome

  2016cites this paper
• THE TUMOR CELL IDENTITY: A GATEWAY TO THE MOLECULAR BASIS OF MALIGNANT TRANSFORMATION

  2016cites this paper
• Micro-RNAs in the parathyroid: a new portal in understanding secondary hyperparathyroidism

  2016cites this paper
• Dissecting New Molecular Mechanisms in Thyroid Diseases Using Genetically Modified Mouse Models

  2016influential citation
• Progress in micro RNA focused research in endocrinology

  2016cites this paper
• Chapter 73 – Anatomy and Development of the Thyroid

  2016cites this paper
• Epithelialization of mouse ovarian tumor cells originating in the fallopian tube stroma

  2016cites this paper
• miRNA expression and function in thyroid carcinomas: a comparative and critical analysis and a model for other cancers

  2016cites this paper
• Mice lacking microRNAs in Pax8-expressing cells develop hypothyroidism and end-stage renal failure

  2016influential citation
• MicroRNA biogenesis and cellular proliferation.

  2015cites this paper
• Thyrocyte-specific Dicer1 deficiency alters thyroid follicular organization and prevents goiter development.

  2015cites this paper
• Selective Dicer Suppression in the Kidney Alters GSK3β/β-Catenin Pathways Promoting a Glomerulocystic Disease

  2015influential citation
• Thyroid transcription factors in development, differentiation and disease

  2015cites this paper
• The miRNA-mediated cross-talk between transcripts provides a novel layer of posttranscriptional regulation.

  2014cites this paper
• Deregulation of microRNA expression in thyroid tumors

  2014cites this paper
• Deregulation of microRNA expression in thyroid neoplasias

  2014cites this paper
• MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale

  2014cites this paper
• MicroRNA in Teleost Fish

  2014cites this paper
• Dicer Expression Exhibits a Tissue-Specific Diurnal Pattern That Is Lost during Aging and in Diabetes

  2013cites this paper
• Mechanisms of thyroid development and dysgenesis: an analysis based on developmental stages and concurrent embryonic anatomy.

  2013cites this paper
• Estudo dos genes DICER1 e C8orf48 em formas familiares de bócio multinodular e cancro da tiróide

  2013cites this paper
• Reciprocal epithelial:endothelial paracrine interactions during thyroid development govern follicular organization and C-cells differentiation.

  2013cites this paper
• The RNase III Enzyme DROSHA Is Essential for MicroRNA Production and Spermatogenesis*

  2012cites this paper
• The Rnase Iii Enzyme Drosha Is Essential for Microrna Production and Spermatogenesis * □ S

  year unknowncites this paper