Splicing isoform-specific functional genomic in cancer cells

Brosseau, Jean-Philippe

doi:10.1186/s41241-018-0068-6

Applied Cancer Research

Table 2 Phenotypic analysis of human cancer cell lines transfected with SM targeting cancer-related genes

From: Splicing isoform-specific functional genomic in cancer cells

Gene	ASE type	Backbone chemistry	Relative location	Splicing effect	Phenotype	Ref.
MDM2	cassette	PNA	Spanning the 3’ss intron-exon junction	Promote intron retention and exon exclusion	Sensitize JAR cells to camptothecin	[81]
PRKCD	Alt5’	2’-MOE-PS	Covering the proximal 5’ss	Promote usage of the distal 5’ss	Induce apoptosis in NT2 cells	[68]
FLT1 (VEGFR1)	cassette	morpholino	Spanning 5’ss exon-intron junction	Induce exon exclusion	Suppress laser-induced choroidal neovascularization	[82]
KDR (VEGFR2)	cassette	morpholino	Spanning 5’ss exon-intron junction	Induce exon exclusion	Suppress laser-induced choroidal neovascularization	[83]
MCL1	cassette	morpholino	Spanning 3’ss intron-exon junction	Induce exon exclusion	Induce apoptosis in BCC and AGS cells	[84]
MCL1	cassette	morpholino	Spanning 5’ss exon-intron junction	Induce exon exclusion	Induce apoptosis in BCC and AGS cells	[84]
VEGF	cassette	morpholino	Spanning 3’ss intron-exon junction	Induce exon exclusion	Induce angiogenesis in PC-3	[85]
TAF6	Alt5’	PS-2’OMe	Fully exonic between both 5;ss	Promote the proximal 5’ss	Induce apoptosis in HeLa cells	[86]
SYK	cassette	2’OMe	Fully exonic	Induce exon exclusion	Induce apoptosis in SKOV3ip1	[43]
ATR	cassette	PS-2’OMe	Fully exonic	Induce exon exclusion	Induce apoptosis of Eu-myc B cells	[58]
EP400	cassette	PS-2’OMe	Fully exonic	Induce exon exclusion	Induce apoptosis of Eu-myc B cells	[58]
DVL1	Intron retention	PS-2’OMe	2 oligonucleotides One Spanning 5’ss exon-intron junction One Spanning 3’ss intron-exon junction	Promote intron retention	Induce apoptosis of Eu-myc B cells	[58]
ERBB4	cassette	LNA, 2’OMe	Fully exonic	Induce exon exclusion	Inhibit growth in MCF7 and T47D	[87]
PKM	Mutually exclusive two exon cassette	PS-2’MOE	Fully exonic	Induce concommittant exon 9 inclusion and exon 10 exclusion	Induce apoptosis in U87-MG and A172 cells	[88]
STAT3	Alt3’	morpholino	Spanning 3’ss intron-exon junction	Promote distal 3’ss	Induce cell death in MDA-MB-435 and MBA-MB-468	[89]
MDM4	cassette	morpholino	Spanning 5’ss exon-intron junction	Induce exon exclusion	Inhibit cell growth in melanoma cell lines	[90]
GLDC	cassette	PS 2’OMe	Fully exonic	Induce exon exclusion	Inhibit cell growth of A549 cells	[91]
USP5	Alt5’	morpholino	Covering the proximal 5’ss	Promote usage of the distal 5’ss	Inhibit cell growth and migration in U251 and LN229	[92]
BRCA1	cassette	morpholino	Fully exonic	Induce exon exclusion	Inhibit cell growth in combination with PARP inhibitor in MCF-7 and MDA-MB-231	[93]
MKNK2	Alt3’	PS-2’MOE and PS-2’OMe	Spanning distal 3’ss junction	Promote proximal 3’ss	Sensitize cells to chemotherapy	[94]
BIM	cassette	PS-2’MOE	Fully exonic	Induce exon exclusion	Restored imatinib-induced apoptosis in KCL22 cells	[95]

The ASE type, backbone chemistry of the oligonucleotide used, Relative location on the ASE, splicing effect and resulting phenotype is described. 2’-MOE 2’ OMethoxyethyl, PS Phosphorothioate, 2’OMe 2’OMethyl, Ref. Reference

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