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DNA was sheared using probe tip sonication and the samples were kept on ice to mitigate heating. Lysates were clarified by centrifugation at 20,000×g for 10 minutes and 100µg of protein for each sample, as determined by BCA, was used for subsequent label-free proteomics. Overnight protein precipitation in acetone at -20°C was performed to produce a protein pellet and the supernatant was discarded. The pellet was washed with ice-cold acetone, air dried for 30 minutes in a fume hood, then resuspended in 100µl of a denaturing buffer containing 8M urea, 400mM aqueous ammonium bicarbonate. Proteins were digested by an in-solution method including disulfide bond reduction (10mM dithiothreitol, 50°C, 30 minutes) and alkylation (20mM iodoacetamide, 25°C, 30 minutes protected from light). The urea concentration was diluted four-fold with high purity water. Proteins were digested overnight with 1µg of trypsin (Promega) at 37°C, followed by acidification with formic acid to halt the digestion. The resulting peptide solution was dried by vacuum centrifugation. Dried peptides were resuspended in 20µl of 0.1% aqueous formic acid and desalted using µ-C18 Ziptips (Millipore Sigma) and dried by vacuum centrifugation. Dried peptides were resuspended in 20µl of 0.1% aqueous formic acid, shaken and sonicated for 10 minutes each, and centrifuged for 5 minutes at 10,000×g."],"repository":["Pride"],"quantification_method":["Not available"],"modification":[""],"data_protocol":["Raw data were processed using FragPipe v22.0 with the LFQ-MBR workflow. Searches were performed against the Human SwissProt database (downloaded September 30, 2024). Variable modifications included lysine and N-terminal acetylation (+42.0106 Da) and methionine oxidation (+15.9949 Da), allowing up to three variable modifications per peptide. DDA+ mode and MSBooster were enabled, and peptide scoring was conducted via the Koina server (https://koina.wilhelmlab.org:443/v2/models/). The resulting msstats.csv file was analyzed with MSstats Shiny v1.6.2 using MSstats v4.12.1. Processing options included log2 transformation of LFQ intensities, removal of runs with over 50% of missing values, imputation of missing values using the accelerated failure time model, and protein summarization with Tukey’s median polish. Statistical testing was performed using a mixed-effects linear model followed by ANOVA-based inference, and potential contaminants were excluded. Data visualization was carried out in R using ggplot2 v3.5.1"],"omics_type":["Proteomics"],"labhead":["Marcus Peter"],"instrument_platform":[""],"submission_type":["PARTIAL"],"labhead_affiliation":["Biochemistry and Molecular Genetics, Hematology and Oncology, Department of Medicine, Northwestern University, USA"],"species":["Homo Sapiens (human)"],"submitter_mail":["peter.faull@northwestern.edu"],"publication":["42306085 Murmann AE, Ebadi M, Patel M, Ewe A, Barajas S, Xiao S, Ko MJ, Lee S, Cai W, Paudel B, Sun L, Bartom ET, Kocherginsky M, Liu Y, Kim DH, Aigner A, Peter ME. Developing a pan cancer therapy based on DISE-inducing short RNAs. Mol Ther Nucleic Acids. 2026 37(2):102963 10.1016/j.omtn.2026.102963"],"submitter_affiliation":["Northwestern University"],"submitter_country":["United States"],"pubmed_abstract":["RNA interference (RNAi) regulates gene expression through small RNAs that act via Argonaute-containing RNA-induced silencing complexes (RISCs). We previously found that short RNAs with G-rich 6mer seeds (e.g., GGGGGC and G5C) can kill cells by targeting C-rich 3' UTR seed matches in essential survival genes (SGs), a mechanism termed death induced by survival gene elimination (DISE). To assess therapeutic potential, we systemically delivered two DISE-inducing sRNAs, sG5C and sCAG (based on CAG trinucleotide repeats), using lipopolyplexes (LPPs) composed of low-molecular-weight polyethyleneimines and lipids. In mouse ovarian and prostate cancer models and a rat hepatocellular carcinoma model, LPP-delivered small RNAs (sRNAs) markedly reduced or eliminated tumors without harming normal tissues. Predicted SG targets were engaged in tumors. Transcriptomic analyses across 10 major human cancers showed that many sG5C-targeted SGs are consistently upregulated in tumors and increase with stage, revealing a therapeutic window. These results support LPP-delivered DISE-inducing sRNAs as a promising pan-cancer therapy."],"pubmed_title":["Developing a pan cancer therapy based on DISE-inducing short RNAs."],"pubmed_authors":["Murmann Andrea E AE, Ebadi Mehrnoosh M, Patel Monal M, Ewe Alexander A, Barajas Sergio S, Xiao Shiyu S, Ko Min Jun MJ, Lee Sanghee S, Cai Wenjie W, Paudel Bidur B, Sun Limin L, Bartom Elizabeth T ET, Kocherginsky Masha M, Liu Yan Y, Kim Dong-Hyun DH, Aigner Achim A, Peter Marcus E ME"],"additional_accession":[]},"is_claimable":false,"name":"Developing a pan cancer therapy based on DISE inducing short RNAs","description":"RNA interference (RNAi) regulates gene expression through small RNAs, including microRNAs (miRNAs) and short interfering RNAs (siRNAs), that function via Argonaute-containing RNA-induced silencing complexes (RISCs). We previously discovered that certain small RNAs (sRNAs) with specific 6mer G-rich seed sequences (e.g., GGGGGC, or G5C) induce cell death by simultaneously targeting C-rich 3′UTR seed matches in essential survival genes (SGs), a mechanism termed Death Induced by Survival gene Elimination (DISE). Tumor-suppressive miRNAs (e.g., miR-34a-5p, miR-15/16-5p) harness this mechanism to selectively kill cancer cells, while sparing normal cells due to their unique seed composition. To evaluate therapeutic potential, we used lipopolyplexes (LPPs) formulated with tyrosine-modified low-molecular-weight polyethyleneimines and lipids to systemically deliver two classes of DISE-inducing sRNAs (Di-sRNAs): sG5C and sCAG (based on CAG trinucleotide repeats). In mouse models of ovarian cancer (OC), prostate cancer (PC), and a hepatocellular carcinoma (HCC) rat model, LPP-mediated delivery of Di-sRNAs significantly suppressed or eliminated tumors without adverse effects on normal tissues. We confirmed on-target engagement of predicted SGs in tumors. Furthermore, transcriptomic analyses across 10 major human cancers revealed that many sG5C-targeted SGs are consistently upregulated in tumors compared to normal tissues, with expression increasing with cancer stage highlighting a therapeutic window for selective targeting. These findings demonstrate the potential of LPP-delivered Di-sRNAs as a pan-cancer therapeutic strategy that exploits intrinsic differences in survival gene expression between cancerous and normal tissues. This work lays the foundation for the development of G-rich seed-based sRNAs as a broadly effective, mechanism-based anticancer 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