Dewaele, Shanna

Mestdagh, Pieter

Vanderheyden, Katrien

Vandesompele, Jo

English

Ghent University Academic Bibliography

Shanna	Dewaele		THERAPEUTIC	APPLICATIONS	OF	SAMMSON	LNCRNA	INHIBITION	IN	UVEAL	MELANOMA		Shanna	Dewaele	(1,2),	Katrien	Vanderheyden	(1,2),	Jo	Vandesompele	(1,2),	Pieter	Mestdagh	(1,2)		(1) Center	for	Medical	Genetics,	Ghent	University,	Ghent,	Belgium	(2) Cancer	Research	Institute	Ghent	(CRIG),	Ghent	University,	Ghent,	Belgium		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	 8	 representative	 cell	 lines	 with	 SAMMSON-specific	 ASOs	 and	 observed	 a	strong	 reduction	 in	 cell	 viability,	 accompanied	 by	 induction	 of	 apoptosis.	 In	 line	 with	 the	 role	 of	SAMMSON	in	modulating	mitochondrial	metabolism,	SAMMSON	knock	down	resulted	in	decreased	mitochondrial	oxygen	consumption.		Uveal	melanomas	are	characterized	by	activated	MEK-signaling	through	mutations	in	GNA11/GNAQ.	Combining	SAMMSON-specific	ASOs	with	 the	MEK-inhibitor	 Trametinib,	 induced	 strong	 synergistic	effects,	 resulting	 in	 a	 nearly	 complete	 abrogation	 of	 tumor	 cells	 at	 nanomolar	 concentrations	 of	Trametinib.	 The	 in	 vivo	 effects	 of	 SAMMSON	 inhibition,	 whether	 or	 not	 in	 combination	 with	Trametinib,	are	currently	being	investigated	in	a	uveal	melanoma	PDX	model.	Together,	our	results	demonstrate	the	efficacy	of	SAMMSON	inhibition	as	a	novel	treatment	option	for	 uveal	 melanoma	 and	 demonstrate	 its	 synergism	 with	 MEK	 inhibition	 making	 SAMMSON	 a	promising	anti-cancer	target	for	uveal	melanoma	patients.					

Therapeutic applications of SAMMSON lncRNA inhibition in uveal melanoma

https://biblio.ugent.be/publication/8546043/file/8546046.pdf

Therapeutic applications of SAMMSON lncRNA inhibition in uveal melanoma

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Ghent University Academic Bibliography