Targeting nonsense-mediated mRNA decay in colorectal cancers with microsatellite instability

a Microarray analysis of NMD-related factors in MSI/MSS tumor tissues ([MSS primary CRC], n？=？48; [MSI primary CRC], n？=？40). b Microarray analysis associated with Exome sequencing data of 30 MSI tumors to compare the expression of genes with mutation in microsatellite located in the last exon (LE; n？=？98) or before the last exon (NLE; n？=？569). c Schematic structure of mutant proteins (15 mutated tumor suppressor genes in green or 16 mutated oncogenes in red) with NLE mutations and significant down-regulation in MSI tumors. d Left panel: relative expression levels of HSP110wt and HSP110DE9 mRNAs by quantitative RT-PCR in MSS and MSI CRC primary tumors. No Del (wild type status; MSS CRCs) n？=？36; DelS (small deletion: ≤4？pb; MSI CRCs), n？=？28; DelL (large deletion: >4 pb; MSI CRCs), n？=？7. Right panel: relative mRNA expression levels of HSP110wt and HSP110DE9 determined by quantitative RT-PCR in MSS and MSI CRC cell lines. No T17 deletion [No Del], n？=？6 CRC cell lines (ISI, SW1116, V9P, ALA, FET, SW480); small T17 Deletion [DelS], n？=？4 CRC cell lines (HCT8, HCT116, TC71, LIM1215); large T17 Deletion [DelL], n？=？6 CRC cell lines (TC7, Lovo, KM12, LS411, Ls174T, Co115). Data are means？±？SEM. e Quantification of all HSP110 mRNAs. Densities and bar plots of HSP110 log2 intensities in normal colonic mucosa (Muc), adenomas (Ade), MSS tumors (MSS), and MSI tumors (MSI). All Data are means？±？SEM. Unpaired t-test was performed to determine significance. **p？<？0.01, ***p？<？0.001, ****p？<？0.000