BET bromodomain inhibitor JQ1 modulates microRNA expression in thyroid cancer cells

  • Authors:
    • Catia Mio
    • Ketty Conzatti
    • Federica Baldan
    • Lorenzo Allegri
    • Marialuisa Sponziello
    • Francesca Rosignolo
    • Diego Russo
    • Sebastiano Filetti
    • Giuseppe Damante
  • View Affiliations

  • Published online on: December 12, 2017     https://doi.org/10.3892/or.2017.6152
  • Pages: 582-588
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Abstract

Anaplastic thyroid carcinoma (ATC) represents the most lethal thyroid cancer sub-type, currently unresponsive to standard treatments. Recently, bromodomain and extra-terminal (BET) proteins have emerged as attractive therapeutic targets in several diseases, including cancer. In different cancer models, the anti-neoplastic activity of BET inhibitors such as JQ1, I-BET762 and I-BET151 have already been established, due to both direct and indirect effects. miRNAs are 20-22 nucleotide transcriptional regulators which play important roles in proliferation, differentiation and apoptosis. Hitherto, the relationship between JQ1 and miRNAs has not been explored. The goal of this study was to delineate JQ1-associated miRNA regulation in ATC cells. Two ATC-derived cell lines (SW1736 and 8505c) were treated with either 5 µM JQ1 or vehicle for 48 or 72 h. A non-tumorigenic thyroid cell line (Nthy-ori 3-1) was used as a control. miRNome analysis displayed a JQ1-related dysregulation of several miRNAs, 7 of which turned out to be commonly dysregulated in both cell lines at both time-points. Furthermore, miR-4516 turned out to be downregulated in both ATC cell lines, when compared to the non-tumorigenic ones and notably, JQ1 treatment in both ATC cell lines induced its upregulation, restoring, in some way, its basal expression levels. We, therefore, focused on miR-4516 expression and STAT3 levels, since it was previously predicted to be a putative target of this microRNA. Consistently, phospho-STAT3 and its target p21Waf1/Cip1 turned out to be downregulated and upregulated in both JQ1-treated ATC cell lines, respectively. Thus, our data revealed that modulation of miRNA expression is one of the multiple mechanisms of the effect of JQ1 in thyroid cancer cells.
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February-2018
Volume 39 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Mio C, Conzatti K, Baldan F, Allegri L, Sponziello M, Rosignolo F, Russo D, Filetti S and Damante G: BET bromodomain inhibitor JQ1 modulates microRNA expression in thyroid cancer cells. Oncol Rep 39: 582-588, 2018
APA
Mio, C., Conzatti, K., Baldan, F., Allegri, L., Sponziello, M., Rosignolo, F. ... Damante, G. (2018). BET bromodomain inhibitor JQ1 modulates microRNA expression in thyroid cancer cells. Oncology Reports, 39, 582-588. https://doi.org/10.3892/or.2017.6152
MLA
Mio, C., Conzatti, K., Baldan, F., Allegri, L., Sponziello, M., Rosignolo, F., Russo, D., Filetti, S., Damante, G."BET bromodomain inhibitor JQ1 modulates microRNA expression in thyroid cancer cells". Oncology Reports 39.2 (2018): 582-588.
Chicago
Mio, C., Conzatti, K., Baldan, F., Allegri, L., Sponziello, M., Rosignolo, F., Russo, D., Filetti, S., Damante, G."BET bromodomain inhibitor JQ1 modulates microRNA expression in thyroid cancer cells". Oncology Reports 39, no. 2 (2018): 582-588. https://doi.org/10.3892/or.2017.6152