PXD069011

PXD069011 is an original dataset announced via ProteomeXchange.

Title	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 therapy.
HostingRepository	PRIDE
AnnounceDate	2026-06-29
AnnouncementXML	Submission_2026-06-28_16:45:10.453.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Peter Faull
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-30 11:46:29	ID requested
⏵ 1	2026-06-28 16:45:11	announced

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, 37(2):102963(2026) [pubmed]

10.1016/j.omtn.2026.102963;

submitter keyword: RNAi, DISE, lipopolyplexes

Marcus Peter
contact affiliation	Biochemistry and Molecular Genetics, Hematology and Oncology, Department of Medicine, Northwestern University, USA
contact email	m-peter@northwestern.edu
lab head
Peter Faull
contact affiliation	Northwestern University
contact email	peter.faull@northwestern.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD069011

PRIDE project URI

• PRIDE
  1. PXD069011
     1. Label: PRIDE project
     2. Name: Developing a pan cancer therapy based on DISE inducing short RNAs