The long non-coding RNA SAMMSON is essential for uveal melanoma cell survival

Autor: Jo Vandesompele, Justine Nuytens, Aart G. Jochemsen, Didier Decaudin, Fariba Nemati, Jilke De Wilde, Manuel Rodrigues, Rudy Van Coster, Eleonora Leucci, Joél Smet, Louis Delhaye, Peihua Zhao, Shanna Dewaele, Pieter Mestdagh, Jasper Anckaert, Sven Eyckerman, Katrien Vanderheyden, Eric James de Bony, Maxime Verschoore, Boel De Paepe, Jo Van Dorpe, Jean-Christophe Marine, Nurten Yigit, Eveline Vanden Eynde
Rok vydání: 2021
Předmět:
Zdroj: Oncogene
ONCOGENE
ISSN: 1476-5594
0950-9232
DOI: 10.1038/s41388-021-02006-x
Popis: Long non-coding RNAs (lncRNAs) can exhibit cell-type and cancer-type specific expression profiles, making them highly attractive as therapeutic targets. Pan-cancer RNA sequencing data revealed broad expression of the SAMMSON lncRNA in uveal melanoma (UM), the most common primary intraocular malignancy in adults. Currently, there are no effective treatments for UM patients with metastatic disease, resulting in a median survival time of 6–12 months. We aimed to investigate the therapeutic potential of SAMMSON inhibition in UM. Antisense oligonucleotide (ASO)-mediated SAMMSON inhibition impaired the growth and viability of a genetically diverse panel of uveal melanoma cell lines. These effects were accompanied by an induction of apoptosis and were recapitulated in two uveal melanoma patient derived xenograft (PDX) models through subcutaneous ASO delivery. SAMMSON pulldown revealed several candidate interaction partners, including various proteins involved in mitochondrial translation. Consequently, inhibition of SAMMSON impaired global, mitochondrial and cytosolic protein translation levels and mitochondrial function in uveal melanoma cells. The present study demonstrates that SAMMSON expression is essential for uveal melanoma cell survival. ASO-mediated silencing of SAMMSON may provide an effective treatment strategy to treat primary and metastatic uveal melanoma patients.
Databáze: OpenAIRE
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