2. Academic Validation
  3. The HuR CMLD-2 inhibitor exhibits antitumor effects via MAD2 downregulation in thyroid cancer cells

The HuR CMLD-2 inhibitor exhibits antitumor effects via MAD2 downregulation in thyroid cancer cells

  • Sci Rep. 2019 May 14;9(1):7374. doi: 10.1038/s41598-019-43894-0.
Lorenzo Allegri 1,  Federica Baldan 2,  Sudeshna Roy 3,  Jeffrey Aubé 4,  Diego Russo 5,  Sebastiano Filetti 6,  Giuseppe Damante 1
Affiliations

Affiliations

  • 1 Department of Medical Area, University of Udine, 33100, Udine, Italy.
  • 2 Department of Translational and Precision Medicine, University of Roma 'Sapienza', 06100, Roma, Italy. federica.baldan12@gmail.com.
  • 3 Department of BioMelecular Sciences, School of Pharmacy, University of Mississippi, 413 Faser Hall, Mississippi, 38677-1848, USA.
  • 4 Division of Chemical Biology and Medical Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, North Carolina, 27599-7363, USA.
  • 5 Department of Health Sciences, University of Catanzaro "Magna Graecia", 88100, Catanzaro, Italy.
  • 6 Department of Translational and Precision Medicine, University of Roma 'Sapienza', 06100, Roma, Italy.
PMID: 31089242 DOI: 10.1038/s41598-019-43894-0
Abstract

Hu antigen R (HuR) is indeed one of the most studied RNA-binding protein (RBP) since its fundamental role both in tumorigenesis and Cancer progression. For this reason, downregulation in HuR protein levels or inhibition of HuR biological function are, nowadays, attractive goals in Cancer research. Here, we examined the antitumor effects of CMLD-2 in four thyroid Cancer cell lines (SW1736, 8505 C, BCPAP and K1). Indeed, CMLD-2 competitively binds HuR protein disrupting its interaction with RNA-targets. 35 μM CLMD-2 produced a significant downregulation in thyroid Cancer cell viability, coupled to an increase in Apoptosis. Moreover, CMLD-2 treatment hindered both migration and colony formation ability. MAD2 is a microtubules-associated protein known to be greatly overexpressed in Cancer and correlating with tumor aggressiveness. Furthermore, MAD2 is known to be a HuR target. CMLD-2 treatment induced a strong MAD2 downregulation and rescue experiments depicted it as a key effector in HuR-mediated in Cancer. Altogether, these data contributed to foster HuR inhibition as valid antineoplastic treatment in thyroid Cancer, highlighting MAD2 as a novel therapeutic target.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-124828
    98.99%, HuR-ARE Interaction Inhibitor
    HuR