BRAFV600E Mutation-Responsive miRNA-222-3p Promotes Metastasis of Papillary Thyroid Cancer Cells via Snail-Induced EMT
BRAF 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...
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Published in | Frontiers in endocrinology (Lausanne) Vol. 13; p. 843334 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
16.05.2022
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Subjects | |
Online Access | Get full text |
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Summary: | BRAF
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
BRAF
mutation remained unclear. Here, we identified significant up-regulation of miR-222-3p in PTC tissues harboring
BRAF
V600E
mutation compared with BRAF wild type (
BRAF
WT
) 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
V600E
oncoprotein increased the expression of miR-222-3p in B-CPAP and TPC-1 cells. The treatment of BRAF
V600E
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
via
the Snail transcription factor. Immunohistochemistry (IHC) analysis demonstrated the up-regulation of Snail correlated with lymph node metastasis and
BRAF
V600E
mutation in PTC. Besides,
in situ
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Edited by: Joachim Feldkamp, Bielefeld University, Germany Reviewed by: Khawla S. Al-Kuraya, King Faisal Specialist Hospital & Research Centre, Saudi Arabia; Loris Bertazza, University of Padua, Italy These authors have contributed equally to this work and shared first authorship This article was submitted to Cancer Endocrinology, a section of the journal Frontiers in Endocrinology |
ISSN: | 1664-2392 1664-2392 |
DOI: | 10.3389/fendo.2022.843334 |