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Endocrine

, Volume 65, Issue 3, pp 582–594 | Cite as

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

  • 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 SalvatoreEmail author
Original Article
  • 138 Downloads

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.

Keywords

miR-650 PPP2CA Thyroid cancer Motility 

Notes

Acknowledgements

We thank Gennaro Di Maro for its contribution in q-RT-PCR studies.

Funding

This study was funded by grants: “Bando di Ateneo per il sostegno alla partecipazione ai bandi di ricerca individuale (quota A per l’anno 2016 e 2017) e ricerca competitiva (quota C per l’anno 2016)” (code DSMB187) from University of Naples “Parthenope” to GS and SO, by 5 × 1000 IRCCS SDN (2013) and by Legge 5/2002 (Annualità 2007) Regione Campania.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12020_2019_1910_MOESM1_ESM.docx (48 kb)
Supplementary Table 1
12020_2019_1910_MOESM2_ESM.pdf (151 kb)
Supplementary Table 2
12020_2019_1910_MOESM3_ESM.pdf (57 kb)
Supplementary Table 3
12020_2019_1910_MOESM4_ESM.docx (7 mb)
Supplementary information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Francesca Maria Orlandella
    • 1
  • Raffaela Mariarosaria Mariniello
    • 2
    • 3
  • Paola Lucia Chiara Iervolino
    • 1
  • Esther Imperlini
    • 1
  • Annalisa Mandola
    • 2
    • 3
  • Anna Verde
    • 2
  • Anna Elisa De Stefano
    • 2
    • 3
  • Katia Pane
    • 1
  • Monica Franzese
    • 1
  • Silvia Esposito
    • 2
  • Fulvio Basolo
    • 4
  • Stefania Orrù
    • 1
    • 3
  • Giuliana Salvatore
    • 1
    • 3
    Email author
  1. 1.IRCCS SDN, NapoliNapoliItaly
  2. 2.CEINGE - Biotecnologie Avanzate s.c. a r.l.NapoliItaly
  3. 3.Dipartimento di Scienze Motorie e del BenessereUniversità “Parthenope”NapoliItaly
  4. 4.Dipartimento di Patologia Chirugica, MedicaMolecolare e dell’ Area Critica dell’ Università di PisaPisaItaly

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