Francesca Maria Orlandella1, Raffaela Mariarosaria Mariniello2,3, Paola Lucia Chiara Iervolino1, Esther Imperlini1, Annalisa Mandola2,3, Anna Verde2, Anna Elisa De Stefano2,3, Katia Pane1, Monica Franzese1, Silvia Esposito2, Fulvio Basolo4, Stefania Orrù1,3, Giuliana Salvatore5,6. 1. IRCCS SDN, Napoli, Via Emanuele Gianturco 113, 80143, Napoli, Italy. 2. CEINGE - Biotecnologie Avanzate s.c. a r.l., Via Gaetano Salvatore 486, 80145, Napoli, Italy. 3. Dipartimento di Scienze Motorie e del Benessere, Università "Parthenope", Via Medina 40, 80133, Napoli, Italy. 4. Dipartimento di Patologia Chirugica, Medica, Molecolare e dell' Area Critica dell' Università di Pisa, 56126, Pisa, Italy. 5. IRCCS SDN, Napoli, Via Emanuele Gianturco 113, 80143, Napoli, Italy. giuliana.salvatore@uniparthenope.it. 6. Dipartimento di Scienze Motorie e del Benessere, Università "Parthenope", Via Medina 40, 80133, Napoli, Italy. giuliana.salvatore@uniparthenope.it.
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.
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 humanthyroid 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.
Authors: Ze-Hua Zuo; Yan P Yu; Ying Ding; Silvia Liu; Amantha Martin; George Tseng; Jian-Hua Luo Journal: Am J Pathol Date: 2015-05-05 Impact factor: 4.307
Authors: M Lango-Chavarría; G K Chimal-Ramírez; M E Ruiz-Tachiquín; N A Espinoza-Sánchez; M C Suárez-Arriaga; E M Fuentes-Pananá Journal: Int J Oncol Date: 2017-01-05 Impact factor: 5.650
Authors: Francesca Maria Orlandella; Raffaela Mariarosaria Mariniello; Peppino Mirabelli; Anna Elisa De Stefano; Paola Lucia Chiara Iervolino; Vito Alessandro Lasorsa; Mario Capasso; Rosa Giannatiempo; Maria Rongo; Mariarosaria Incoronato; Francesco Messina; Marco Salvatore; Andrea Soricelli; Giuliana Salvatore Journal: Br J Cancer Date: 2020-05-18 Impact factor: 7.640