{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:22:24Z","timestamp":1787062944064,"version":"build-2736575974"},"reference-count":46,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Loss of the expression of thyroid differentiation markers such as sodium iodide symporter (NIS) and, consequently, radioiodine refractoriness is observed in aggressive papillary thyroid cancer and anaplastic thyroid cancer (ATC) that may harbor the BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                      mutation. Activation of the BRAF\n                      <jats:sup>V600E<\/jats:sup>\n                      oncogene in thyroid follicular cells induces the expression of the\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      cluster that comprises seven mature microRNAs (miRNAs). miRNAs are a class of endogenous small RNAs (\u223c22\u2009nt) that regulate gene expression post-transcriptionally. Indeed,\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      is overexpressed in ATC, and\n                      <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                      prediction shows the potential targeting of thyroid transcription factors and tumor suppressor pathways. In this study, we aimed to investigate the role of the\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      cluster in thyroid cell differentiation and function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      silencing was performed using CRISPR\/Cas9n-guided genomic editing of the\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      gene in the KTC2 ATC cell line, and\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      cluster or individual miRNAs were overexpressed in PCCl3 thyroid cells to evaluate the influence in thyroid cell differentiation and cell function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In this study, we demonstrate that CRISPR\/Cas9n gene editing of the\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      cluster results in promotion of thyroid follicular cell differentiation (NIS, thyroperoxidase, thyroglobulin, PAX8, and NKX2-1 expression) in the KTC2 ATC cell line and inhibits cell migration and proliferation by restoring transforming growth factor beta (TGF-\u03b2) signaling pathway responsiveness. Moreover, induction of the\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      cluster in normal thyroid follicular cells strongly impairs thyroid differentiation and induces a pro-oncogenic effect by blocking TGF-\u03b2 signaling and increasing cell migration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      is a potent regulator of thyroid follicular cell differentiation, and CRISPR\/Cas9n-mediated editing of the\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      gene efficiently blocks\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      expression in the KTC2 ATC cell line, resulting in improvement of thyroid differentiation. Thus, targeting\n                      <jats:italic toggle=\"yes\">miR-17-92<\/jats:italic>\n                      could provide a potential molecular approach to restoring thyroid cell differentiation and NIS expression in aggressive thyroid cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2018.0601","type":"journal-article","created":{"date-parts":[[2019,10,3]],"date-time":"2019-10-03T07:08:07Z","timestamp":1570086487000},"page":"81-94","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":22,"title":["Thyroid Follicular Cell Loss of Differentiation Induced by MicroRNA miR-17-92 Cluster Is Attenuated by CRISPR\/Cas9n Gene Silencing in Anaplastic Thyroid Cancer"],"prefix":"10.1177","volume":"30","author":[{"given":"Cesar Seigi","family":"Fuziwara","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly Cristina","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna Teruko","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21332"},{"key":"e_1_3_5_3_2","first-page":"1454","article-title":"High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET\/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma","volume":"63","author":"Kimura ET","year":"2003","unstructured":"Kimura ET, , Nikiforova MN, , Zhu Z, , Knauf JA, , Nikiforov YE, , Fagin JA. 2003. 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