Newswise — Silencing of the protein-coding gene PRMT5 has possible therapeutic potential for treating Mesothelioma (MM), according to a recent in vitro study published in the Journal of Cellular and Molecular Medicine. The authors evaluated the effects of PRMT5 silencing on mesothelioma cell lines that are characterized as methylthioadenosine phosphorylase (MTAP)-deficient.
Mesothelioma is a very aggressive tumor of the serous membranes mainly associated with asbestos exposure. No effective therapies are currently available and the prognosis is extremely poor. Therefore, there is an urgent need to identify new possible therapeutic approaches.
The research group lead by Antonio Giordano, MD, PhD, Director and Founder of the Sbarro Health Research Organization at Temple University (www.shro.org) in collaboration with the University of Siena, Italy, investigated the therapeutic potential of targeting the Protein Arginine Methyltransferase 5 (PRMT5) enzyme in Methylthioadenosine phosphorylase-deleted (MTAP) MM cells.
MTAP is a key enzyme in the adenine and methionine salvage pathway; it is frequently deleted in MM due to its proximity with CDKN2A, one of the genes most frequently deleted in this malignancy. It has been previously demonstrated that the passenger deletion of MTAP generates a selective vulnerability to PRMT5 inhibition. The researchers demonstrated that PRMT5 silencing slowed MM cell growth and abrogated their clonogenic potential.
This study opens the possibility to individuate a subset of mesothelioma that could be treated with PRMT5 inhibitors.
“Our results are in agreement with previous studies on other cancers and represent a starting point for the evaluation of PRMT5 inhibitors in MTAP-deleted mesothelioma,” says study author Dr. Marcella Barbarino of the University of Siena.
“These promising results can help us to understand the molecular mechanisms underlying the MM's progression and that could be therapeutically exploited,” says Dr. Antonio Giordano.
The study was founded by the Mesothelioma Applied Research Foundation (MARF) and the Sbarro Health Research Organization (SHRO).
Journal Reference: Barbarino M, Cesari D, Bottaro M, Luzzi L, Namagerdi A, Bertolino FM, Bellan C, Proietti F, Somma P, Micheli M, de Santi MM, Guazzo R, Mutti L, Pirtoli L, Paladini P, Indovina P, Giordano A. J Cell Mol Med. 2020 Apr 17. doi: 10.1111/jcmm.15213.