{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:23:42Z","timestamp":1790522622734,"version":"4.1.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Hashimoto\u2019s thyroiditis (TH) is a risk factor for the occurrence of papillary thyroid carcinoma (PTC), which is considered to be the most common type of thyroid cancer. In recent years, the prevalence of PTC with TH has been increasing, but little is known about the genetic alteration in PTC with TH. This study analyzed the mutation spectrum and mutation signature of somatic single nucleotide variants (SNV) for 10 non-tumor and tumor pair tissues of PTC with TH using whole-exome sequencing. The ANK3 protein expression was evaluated by immunohistochemistry in PTC with TH and PTC samples. Moreover, the functional role of ANK3 in PTC cells was determined by CCK-8 proliferation assay, colony formation assays, cell cycle analysis, cell invasion and migration and <jats:italic>in vivo<\/jats:italic> study through overexpression assay. Our results showed three distinct mutational signatures and the C&amp;gt;T\/G&amp;gt;A substitution was the most common type of SNV. Gene-set enrichment analysis showed that most of the significantly mutated genes were enriched in the regulation of actin cytoskeleton signaling. Moreover, <jats:italic>NCOR2, BPTF, ANK3<\/jats:italic>, and <jats:italic>PCSK5<\/jats:italic> were identified as the significantly mutated genes in PTC with TH, most of which have not been previously characterized. Unexpectedly, it was found that ANK3 was overexpressed in cytoplasm close to the membrane of PTC cells with TH and in almost all PTC cases, suggesting its role as a diagnostic marker of PTC. Ectopic expression of <jats:italic>ANK3<\/jats:italic> suppressed invasion and migration, increased apoptosis of B-CPAP and TPC-1 cells. Moreover, our findings revealed that enhanced <jats:italic>ANK3<\/jats:italic> expression inhibits growth of PTC cells both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Ectopic expression of <jats:italic>ANK3<\/jats:italic> significantly enhanced E-cadherin protein expression and inhibited PTC progression, at least in part, by suppression of epithelial-mesenchymal transition (EMT). Our study shows that <jats:italic>ANK3<\/jats:italic> exerts an anti-oncogenic role in the development of PTC and might be an indolent maintainer of PTC.<\/jats:p>","DOI":"10.3389\/fonc.2022.894786","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T07:41:06Z","timestamp":1652341266000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Genetic Alterations in Papillary Thyroid Carcinoma With Hashimoto\u2019s Thyroiditis\uff1a ANK3, an Indolent Maintainer of Papillary Thyroid 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