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10.1038/s41598-017-10318-w

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suck abstract from ncbi


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pmid28855631
      Sci+Rep 2017 ; 7 (1 ): 9942
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  • Functional analysis of a novel, thyroglobulin-embedded microRNA gene deregulated in papillary thyroid carcinoma #MMPMID28855631
  • Kolanowska M ; Wójcicka A ; Kubiak A ; ?wierniak M ; Kotlarek M ; Maci?g M ; Gaj P ; Koperski ? ; Górnicka B ; Ja?d?ewski K
  • Sci Rep 2017[Aug]; 7 (1 ): 9942 PMID28855631 show ga
  • MicroRNAs, non-coding regulators of gene expression, are known culprits of thyroid cancer. Using next-generation sequencing, we identified a novel microRNA gene, encoded within an important thyroid regulator - thyroglobulin, and analyzed its functionality in the thyroid gland. In vitro and in silico analyses proved that the novel miR-TG is processed from the precursor, and co-expressed with thyroglobulin. Both genes are specific for thyroid tissue and downregulated in papillary thyroid carcinoma by 44% (p?=?0.04) and 48% (p?=?0.001), respectively. Putative target genes for miR-TG were identified using in silico tools, which pinpointed MAP4K4, an oncogene upregulated in thyroid cancer. Analysis of transcriptome by RNA-seq revealed that overexpression of miR-TG in PTC-derived cell line led to downregulation of several genes, including MAP4K4 (fold change 0,82; p?=?0.036). The finding was confirmed by SQ-PCR (fold change 071; p?=?0.004). Direct interaction between miR-TG and MAP4K4 was confirmed in the luciferase assay (p?=?0.0006). Functional studies showed increase proliferation in K1 cell line transfected with miR-TG. We propose that in normal thyroid miR-TG plays a fine-tuning effect on the maintenance of MAPK pathway, inhibiting the expression of miR's target MAP4K4. This regulation is disturbed in cancer due to downregulation of the novel, thyroglobulin-embedded microRNA, characterized in this study.
  • |*Down-Regulation [MESH]
  • |3' Untranslated Regions [MESH]
  • |Cell Line, Tumor [MESH]
  • |Computer Simulation [MESH]
  • |Gene Expression Regulation, Neoplastic [MESH]
  • |HeLa Cells [MESH]
  • |High-Throughput Nucleotide Sequencing/methods [MESH]
  • |Humans [MESH]
  • |Intracellular Signaling Peptides and Proteins/*genetics [MESH]
  • |MicroRNAs/*genetics/metabolism [MESH]
  • |Organ Specificity [MESH]
  • |Protein Serine-Threonine Kinases/*genetics [MESH]
  • |Sequence Analysis, RNA [MESH]
  • |Thyroglobulin/*genetics/metabolism [MESH]
  • |Thyroid Cancer, Papillary/*genetics [MESH]
  • |Thyroid Gland/metabolism [MESH]


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