Department of Genetics and Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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long-term surveillance for 25% of patients due to the presence of thyroglobulin antibody. In FNA-aspirated cells, about 30% of thyroid gland biopsies remain undecided or undiagnosed [ 6 ]. Tumors of molecular markers such as miRNA are generated by
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depending on their length into long ncRNAs (lncRNAs) and short ncRNAs (e.g. miRNA, piRNAs). Based on their function, ncRNAs are classified into infrastructural (e.g. snRNA, snoRNAs, and rRNAs) and regulatory ncRNAs (e.g. miRNA, lncRNAs, piRNAs, and siRNAs
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Instituto Nacional de Cancer (INCA), Rio de Janeiro, Brazil
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Introduction MicroRNAs (miRNAs) are small noncoding RNA molecules of 19-22 nucleotides in length that are capable of regulating gene expression at a translational level and binding to a complementary sequence found in the 3′-untranslated
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physiological and/or pathological cardiac remodeling [ 1 , 3 ]. Stimulation and repression of gene expression are the result of direct transcriptional effects as well as regulation of translation efficiency by microRNAs (miRNAs) [ 4 , 5 ]. In the case of
Department of Women’s and Children’s Health, Pediatric Endocrinology Unit, Padua University Hospital, Padua, Italy
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immunosuppressive treatment is between 50 and 80% according to published trials ( 7 ). For this reason, where first-line GC therapies fail, other second-line treatments are available, such as rituximab, tocilizumab or teprotumumab (only in the USA). miRNAs are
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Objective: Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by inflammation, fibrosis and accumulation of fatty acids in the liver. MASH disease progression has been associated with reduced thyroid hormone (TH) signalling in the liver, including reduced expression of deiodinase type I (DIO1) and TH receptor beta (THRB). However, the underlying mechanisms mediating these effects remain elusive. Here, we hypothesized, that epigenetic mechanisms may be involved in modulating hepatic TH action.
Methods: Liver samples from patients with and without MASH were analyzed by qRT-PCR and correlated with clinical parameters. Luciferase reporter assays and overexpression of miRNA in HepG2-cells were used to validate functional binding of miRNA to predicted targets. DNA-methylation was analyzed by bisulfite-pyrosequencing.
Results: miR-34a-5p was upregulated in MASH patients and correlated positively with clinical parameters of MASH. Using in silico and in vitro analysis we demonstrate that miR-34a-5p is capable of targeting several modulators of local hepatic TH action, as evidenced by functional binding of miR-34a-5p to the seed sequence in the THRB and DIO1 genes. Consequently, overexpression of miR-34a-5p in HepG2-cells reduced the expression of THRA, THRB, DIO1 and SLC10A1, thus potentially mediating an acquired hepatic resistance to TH in MASH. As additional regulatory mechanism, DNA-methylation of THRB intron 1 was increased in MASH and negatively correlated with THRB expression.
Conclusion: miR-34a-5p constitutes a possible epigenetic master regulator of hepatic TH action, which together with THRB specific DNA-methylation could explain a possible developing TH resistance in the liver during MASH progression on the molecular level.
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Department of Medicine, University of Alcalá de Henares, Madrid
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IdiSNA (Instituto de investigación en la salud de Navarra), Pamplona, Spain
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-related mutations. The ThyroSeq approach has been proposed as a “rule-in” test [ 16 , 17 , 18 ], that is, a test with a high specificity. - Rossetta genomics is a platform recently developed that analyses the expression of a combination of micro-RNA (miRNA
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], targeted next-generation sequencing (tNGS) [ 12 ], and the combination of mutation detection and miRNA expression [ 13 ], have been reported as promising in ruling in or out a substantial risk of cancer. Of note, the major limit to the use of molecular
Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria, Modena, Italy
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Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
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Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
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Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria, Modena, Italy
Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy
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Center for Genomic Research, University of Modena and Reggio Emilia, Modena, Italy
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of Let-7 and risk of papillary thyroid carcinoma: a case-control study . Medicine 2015 94 e1879. ( https://doi.org/10.1097/MD.0000000000001879 ) 58 Perdas E Stawski R Kaczka K Zubrzycka M . Analysis of Let-7 family miRNA in plasma as
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Department of Human Genetics, McGill University, Montreal, Québec, Canada
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Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Subiaco, Washington, Australia
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King Edward Memorial Hospital, Perth, Washington, Australia
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Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Washington, Australia
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Department of Human Genetics, McGill University, Montreal, Québec, Canada
Department of Medical Genetics,
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Faculty of Health and Medical Sciences, School
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precursors to generate mature microRNAs (miRNAs), which, in turn, post-transcriptionally regulate gene expression. Carriers of DICER1 mutations are predisposed to developing a broad range of tumours of predominantly paediatric or adolescent onset [ 17 ], as