De Paepe, Boel

Decaudin, Didier

Delhaye, Louis

Dewaele, Shanna

Eyckerman, Sven

Mestdagh, Pieter

Nemati, Fariba

Van Coster, Rudy

Vanderheyden, Katrien

Vandesompele, Jo

English

Ghent University Academic Bibliography

Therapeutic applications of SAMMSON lncRNA inhibition in uveal melanoma  Shanna Dewaele1,2, Katrien Vanderheyden1,2, Boel De Paepe3, Louis Delhaye2,4, Fariba Nemati5, Didier Decaudin5, Sven Eyckerman2,4, Rudy Van Coster3, Jo Vandesompele1,2 and Pieter Mestdagh1,2  1 Center for Medical Genetics, Ghent University, Ghent, Belgium 2 Cancer Research Institute Ghent (CRIG), Ghent University, Ghent, Belgium 3 Department of Pediatrics, Division of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium 4 Center for Medical Biotechnology, VIB-Ghent University, Ghent, Belgium 5 Translational Research Department, Institut Curie, PSL Research University, Paris, France  Uveal melanoma is the most common intraocular malignancy in adults. The lack of an effective treatment results in a median survival time less than one year for patients with metastatic disease. Recently, our lab identified the melanoma-specific long non-coding RNA (lncRNA) SAMMSON as a novel therapeutic target in skin melanoma. Analysis of a PAN cancer RNA-sequencing dataset revealed consistent expression of SAMMSON in uveal melanoma tumors. Although SAMMSON expression was lower in uveal compared to skin melanoma, over 90% of uveal melanoma tumors showed detectable SAMMSON expression. Further analysis also revealed SAMMSON expression in conjunctival melanoma, another form of ocular melanoma. To evaluate the therapeutic potential of SAMMSON inhibition in uveal and conjunctival melanoma, we treated a panel of representative cell lines with SAMMSON-specific antisense oligonucleotides (ASOs) and observed a strong reduction in cell viability, accompanied by induction of apoptosis. These effects were dependent on ASO dosing and were validated using 8 independent SAMMSON-targeting ASOs and various ASO chemistries. ASO-treatment of a uveal melanoma PDX model further confirmed the observed phenotype. In line with the function of SAMMSON in modulating mitochondrial metabolism, SAMMSON knock down resulted in a decreased mitochondrial oxidative phosphorylation. Together, our results demonstrate the efficacy of SAMMSON inhibition as a novel treatment option for uveal melanoma patients.     

Therapeutic applications of SAMMSON lncRNA inhibition in uveal melanoma

https://biblio.ugent.be/publication/8642798/file/8642801

Therapeutic applications of SAMMSON lncRNA inhibition in uveal melanoma

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Ghent University Academic Bibliography