miR-650 promotes motility of anaplastic thyroid cancer cells by targeting PPP2CA View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03-29

AUTHORS

Francesca Maria Orlandella, Raffaela Mariarosaria Mariniello, Paola Lucia Chiara Iervolino, Esther Imperlini, Annalisa Mandola, Anna Verde, Anna Elisa De Stefano, Katia Pane, Monica Franzese, Silvia Esposito, Fulvio Basolo, Stefania Orrù, Giuliana Salvatore

ABSTRACT

PURPOSE: Aberrant expression of miRNAs is crucial in several tissues tumorigenesis including thyroid. Recent studies demonstrated that miR-650 plays different role depending on the cancer type. Herein, we investigated the role of miR-650 in thyroid carcinoma. METHODS: The expression of miR-650 was analyzed in human thyroid tissues by q-RT-PCR. Anaplastic (8505C, CAL62, SW1736) and papillary (TPC-1) thyroid cancer cell lines were used to dissect the role of miR-650 on malignant hallmarks of transformation. Label-free proteomic analysis was exploited to unravel the targets of miR-650, while luciferase reporter assay and functional experiments were performed to confirm a selected target. Spearman's rank correlation test was used to assess the association between miR-650 and its target in human thyroid cancer tissues. RESULTS: miR-650 is over-expressed in anaplastic (ATC) thyroid carcinoma where it enhances cell migration and invasion. Proteomic label-free and bioinformatics analysis revealed that the serine-threonine protein phosphatase 2 catalytic subunit alpha (PPP2CA) is a target of miR-650; these finding were confirmed by luciferase assay. Restoration of PPP2CA mRNA, deprived of its 3'UTR, is able to revert the malignant phenotype induced by miR-650 in HEK-293 cells. Importantly, PPP2CA is down-regulated in ATC tissues and is inversely correlated with miR-650. CONCLUSIONS: miR-650 displayed oncogenic activity in ATC cells through targeting PPP2CA phosphatase. These results suggest that miR-650/PPP2CA axis could be modulated to interfere with motile ability of thyroid carcinoma cells. More... »

PAGES

1-13

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s12020-019-01910-3

    DOI

    http://dx.doi.org/10.1007/s12020-019-01910-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1113101972

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30927143


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