1. Small interfering RNAs based on huntingtin trinucleotide repeats are highly toxic to cancer cells
Ten nucleotide Sylamer analysis of the ORFs of genes deregulated in HeyA8 cells transfected with either siCAG/CUG (left) or siCGA/UCG (right) ordered from most downregulated to most upregulated. The three most highly enriched sequences are shown. The 10 nucleotide motifs in bold in the siCAG/CUG analysis correspond to the reverse complement of positions 1–10 and 2–11 in the 19mer siCAG strand. Bonferroni‐adjusted P‐values are shown. Sequences without a P‐value were either not significantly enriched or not at the top of the ranked list. Gene set enrichment analysis for genes containing the CTGCTGCTGC (top panels) or TGCTGCTGCT (bottom panels) sequences identified as enriched in the downregulated genes (see A) in cells transfected with siCAG/CUG when compared to cells transfected with siNT. The analyses were performed with either the ORF (left panels) or the 3′UTR (right panels) of the downregulated genes. P‐values indicate the significance of enrichment. P‐values were calculated using the Kolmogorov–Smirnov test. Correlation between the average of the two viability screens performed in HeyA8 (top panels) or M565 (bottom panels) cells with the percentage of TNRs that are part of 6mer or higher longer repeat sequences in either the ORF (left panels) or 3′UTR (right panel) of the genes. The data points for the six members of TNR family 5 are labeled in blue and those of family 7 are labeled in red. Pearson correlations and P‐values are given. The amino acids that are coded by the targeted triplets in families 5 and 7 Rev.com., reverse component.
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EMBO Rep, Volume: 19, Issue: 3, First published: 12 February 2018, DOI: ( /embr )