{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:13:12Z","timestamp":1785773592720,"version":"3.56.0"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T00:00:00Z","timestamp":1652659200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p><jats:italic>BRAF<\/jats:italic> mutation accounts for 50% of the PTC (papillary thyroid carcinoma) and is closely associated with high-risk clinicopathological characteristics. Increasing evidence implied that dysregulation of miRNA participated in carcinogenesis and progression of cancer. Clinical data showed the significant up-regulation of miR-222-3p in PTC; however, the role of miR-222-3p and possible relationship with <jats:italic>BRAF<\/jats:italic> mutation remained unclear. Here, we identified significant up-regulation of miR-222-3p in PTC tissues harboring <jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic> mutation compared with BRAF wild type (<jats:italic>BRAF<jats:sup>WT<\/jats:sup><\/jats:italic>) from collected PTC clinical samples. External validation performed with The Cancer Genome Atlas (TCGA) databases was consistent with the above result. Exogenous expression of BRAF<jats:sup>V600E<\/jats:sup> oncoprotein increased the expression of miR-222-3p in B-CPAP and TPC-1 cells. The treatment of BRAF<jats:sup>V600E<\/jats:sup> and MEK inhibitor, PLX4720 and PD0325901, decreased the expression of miR-222-3p in B-CPAP but not in TPC-1. Inhibition of miR-222-3p significantly suppressed the migration of B-CPAP and induced a mesenchymal-epithelial transition (MET) phenotype <jats:italic>via<\/jats:italic> the Snail transcription factor. Immunohistochemistry (IHC) analysis demonstrated the up-regulation of Snail correlated with lymph node metastasis and <jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic> mutation in PTC. Besides, <jats:italic>in situ<\/jats:italic> hybridization (ISH) and IHC analysis of PTC clinical samples confirmed the correlation between the expression of miR-222-3p and Snail. These results showed miR-222-3p conduced more aggressive clinical manifestation of PTC by promoting Snail-induced EMT.<\/jats:p>","DOI":"10.3389\/fendo.2022.843334","type":"journal-article","created":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T04:53:47Z","timestamp":1652676827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["BRAFV600E Mutation-Responsive miRNA-222-3p Promotes Metastasis of Papillary Thyroid Cancer Cells via Snail-Induced 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