80. Meng L, Ward AJ, Chun S et al (2015) Towards a therapy for Angelman syndrome
by reduction of a long non-coding RNA. Nature 518:409–412. https://doi.org/10.1038/
nature13975
81. Groh M, Lufino MMP, Wade-Martins R, Gromak N (2014) R-loops associated with
triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome.
PLoS Genet 10:e1004318. https://doi.org/10.1371/journal.pgen.1004318
82. Li L, Matsui M, Corey DR (2016) Activating frataxin expression by repeat-targeted
nucleic acids. Nat Commun 7:1–8. https://doi.org/10.1038/ncomms10606
83. Lefebvre S, Buerglen L, Reboullet S et al (1995) Identification and characterization of a
spinal muscular atrophy-determining gene. Cell 80:155–165
84. Lorson CL, Hahnen E, Androphy EJ, Wirth B (1999) A single nucleotide in the SMN
gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci
96:6307–6311. https://doi.org/10.1073/pnas.96.11.6307
85. Burghes AHM, Beattie CE (2009) Spinal muscular atrophy: why do low levels of SMN
make motor neurons sick? Nat Rev Neurosci 10:597–609. https://doi.org/10.1038/nrn2670
86. Touznik A, Maruyama R, Hosoki K et al (2017) LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression
in type 1 SMA fibroblasts. Sci Rep 7:1–9. https://doi.org/10.1038/s41598-017-03850-2
87. Robin V, Griffith G, Carter JPL et al (2017) Efficient SMN rescue following subcutaneous
tricyclo-DNA antisense oligonucleotide treatment. Mol Ther Nucleic Acids 7:81–89. https://
doi.org/10.1016/j.omtn.2017.02.009
88. Finkel RS, Mercuri E, Darras BT et al (2017) Nusinersen versus Sham control in infantileonset spinal muscular atrophy. N Engl J Med 377:1723–1732. https://doi.org/10.1056/
NEJMoa1702752
89. D’Ydewalle C, Ramos DM, Pyles NJ et al (2017) The antisense transcript SMN-AS1 regulates
SMN expression and is a novel therapeutic target for spinal muscular atrophy. Neuron
93:66–79. https://doi.org/10.1016/j.neuron.2016.11.033
90. Woo CJ, Maier VK, Davey R et al (2017) Gene activation of SMN by selective disruption of
lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy. Proc Natl
Acad Sci 114:E1509–E1518. https://doi.org/10.1073/pnas.1616521114
91. Gomes CPC, Spencer H, Ford KL et al (2017) The function and therapeutic potential of
long non-coding RNAs in cardiovascular development and disease. Mol Ther Nucleic Acids
8:494–507. https://doi.org/10.1016/j.omtn.2017.07.014
92. De Majo F, Calore M (2018) Chromatin remodelling and epigenetic state regulation by
non-coding RNAs in the diseased heart. Noncoding RNA Res 3:20–28. https://doi.org/10.
1016/j.ncrna.2018.02.003
93. Hung J, Miscianinov V, Sluimer JC et al (2018) Targeting non-coding RNA in vascular
biology and disease. Front Physiol 9:1–16. https://doi.org/10.3389/fphys.2018.01655
94. Viereck J, Kumarswamy R, Foinquinos A et al (2016) Long noncoding RNA Chast promotes
cardiac remodeling-supplementary materials. Sci Transl Med 8:326ra22. https://doi.org/10.
1126/scitranslmed.aaf1475
95. Modarresi F, Faghihi MA, Lopez-Toledano MA et al (2012) Natural antisense inhibition
results in transcriptional de-repression and gene upregulation. Nat Biotechnol 30:453–459.
https://doi.org/10.1038/nbt.2158
96. Pedram Fatemi R, Salah-Uddin S, Modarresi F et al (2015) Screening for small-molecule
modulators of long noncoding RNA-protein interactions using alphascreen. J Biomol Screen
20:1132–1141. https://doi.org/10.1177/1087057115594187
97. Ding W, Ren J, Ren H, Wang D (2017) Long noncoding RNA HOTAIR modulates MiR-206mediated Bcl-w signaling to facilitate cell proliferation in breast cancer. Sci Rep 7:1–9. https://
doi.org/10.1038/s41598-017-17492-x
98. Li Y, Wang Z, Shi H et al (2016) HBXIP and LSD1 scaffolded by lncRNA hotair mediate
transcriptional activation by c-Myc. Cancer Res 76:293–304. https://doi.org/10.1158/00085472.CAN-14-3607
Altered Long Non-coding RNA Expression in Cancer: Potential Biomarkers. . .
425
by reduction of a long non-coding RNA. Nature 518:409–412. https://doi.org/10.1038/
nature13975
81. Groh M, Lufino MMP, Wade-Martins R, Gromak N (2014) R-loops associated with
triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome.
PLoS Genet 10:e1004318. https://doi.org/10.1371/journal.pgen.1004318
82. Li L, Matsui M, Corey DR (2016) Activating frataxin expression by repeat-targeted
nucleic acids. Nat Commun 7:1–8. https://doi.org/10.1038/ncomms10606
83. Lefebvre S, Buerglen L, Reboullet S et al (1995) Identification and characterization of a
spinal muscular atrophy-determining gene. Cell 80:155–165
84. Lorson CL, Hahnen E, Androphy EJ, Wirth B (1999) A single nucleotide in the SMN
gene regulates splicing and is responsible for spinal muscular atrophy. Proc Natl Acad Sci
96:6307–6311. https://doi.org/10.1073/pnas.96.11.6307
85. Burghes AHM, Beattie CE (2009) Spinal muscular atrophy: why do low levels of SMN
make motor neurons sick? Nat Rev Neurosci 10:597–609. https://doi.org/10.1038/nrn2670
86. Touznik A, Maruyama R, Hosoki K et al (2017) LNA/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression
in type 1 SMA fibroblasts. Sci Rep 7:1–9. https://doi.org/10.1038/s41598-017-03850-2
87. Robin V, Griffith G, Carter JPL et al (2017) Efficient SMN rescue following subcutaneous
tricyclo-DNA antisense oligonucleotide treatment. Mol Ther Nucleic Acids 7:81–89. https://
doi.org/10.1016/j.omtn.2017.02.009
88. Finkel RS, Mercuri E, Darras BT et al (2017) Nusinersen versus Sham control in infantileonset spinal muscular atrophy. N Engl J Med 377:1723–1732. https://doi.org/10.1056/
NEJMoa1702752
89. D’Ydewalle C, Ramos DM, Pyles NJ et al (2017) The antisense transcript SMN-AS1 regulates
SMN expression and is a novel therapeutic target for spinal muscular atrophy. Neuron
93:66–79. https://doi.org/10.1016/j.neuron.2016.11.033
90. Woo CJ, Maier VK, Davey R et al (2017) Gene activation of SMN by selective disruption of
lncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy. Proc Natl
Acad Sci 114:E1509–E1518. https://doi.org/10.1073/pnas.1616521114
91. Gomes CPC, Spencer H, Ford KL et al (2017) The function and therapeutic potential of
long non-coding RNAs in cardiovascular development and disease. Mol Ther Nucleic Acids
8:494–507. https://doi.org/10.1016/j.omtn.2017.07.014
92. De Majo F, Calore M (2018) Chromatin remodelling and epigenetic state regulation by
non-coding RNAs in the diseased heart. Noncoding RNA Res 3:20–28. https://doi.org/10.
1016/j.ncrna.2018.02.003
93. Hung J, Miscianinov V, Sluimer JC et al (2018) Targeting non-coding RNA in vascular
biology and disease. Front Physiol 9:1–16. https://doi.org/10.3389/fphys.2018.01655
94. Viereck J, Kumarswamy R, Foinquinos A et al (2016) Long noncoding RNA Chast promotes
cardiac remodeling-supplementary materials. Sci Transl Med 8:326ra22. https://doi.org/10.
1126/scitranslmed.aaf1475
95. Modarresi F, Faghihi MA, Lopez-Toledano MA et al (2012) Natural antisense inhibition
results in transcriptional de-repression and gene upregulation. Nat Biotechnol 30:453–459.
https://doi.org/10.1038/nbt.2158
96. Pedram Fatemi R, Salah-Uddin S, Modarresi F et al (2015) Screening for small-molecule
modulators of long noncoding RNA-protein interactions using alphascreen. J Biomol Screen
20:1132–1141. https://doi.org/10.1177/1087057115594187
97. Ding W, Ren J, Ren H, Wang D (2017) Long noncoding RNA HOTAIR modulates MiR-206mediated Bcl-w signaling to facilitate cell proliferation in breast cancer. Sci Rep 7:1–9. https://
doi.org/10.1038/s41598-017-17492-x
98. Li Y, Wang Z, Shi H et al (2016) HBXIP and LSD1 scaffolded by lncRNA hotair mediate
transcriptional activation by c-Myc. Cancer Res 76:293–304. https://doi.org/10.1158/00085472.CAN-14-3607
Altered Long Non-coding RNA Expression in Cancer: Potential Biomarkers. . .
425