PXD069826-1

PXD069826 is an original dataset announced via ProteomeXchange.

Title	Proteomic profiling of human colorectal adenocarcinoma Caco-2 cells in response to treatment with mesyl oligonucleotides targeting microRNAs miR-21, miR-155, and miR-17
Description	Colorectal cancer (CRC) ranks among the most aggressive human malignancies and remains a leading cause of cancer mortality globally (Matsuda T. et al., Digestion, 2025). Despite advances in treatment, there is a critical need for novel therapeutic agents that combine high selectivity and minimal toxicity while effectively targeting the molecular mechanisms driving CRC progression. A growing body of evidence highlights the central oncogenic roles of microRNAs miR-21, miR-17, and miR-155 in CRC progression and malignancy (Fu F. et al., Transl Oncol, 2018; Sabry D. et al, Mol Cell Biochem, 2019; Yu W. et al., J Cancer, 2022; Wang D. et al., Cell Death Dis, 2022). Consequently, targeted suppression of these miRNAs through sequence-specific oligonucleotide-based therapeutics represents a promising strategy for simultaneously disrupting multiple carcinogenic pathways. Previous studies have demonstrated the potent anti-oncogenic efficacy of N-(methanesulfonyl)phosphoramidate (mesyl, µ-)-modified antisense oligonucleotides targeting miR-21, miR-155, and miR-17 across various tumor models (Miroshnichenko S. et al, PNAS, 2019; Patutina O. et al., PNAS, 2020, Gaponova (Miroshnichenko) S. et al., Cancers, 2022). In the present investigation, we aimed to elucidate the molecular mechanisms underlying the effects of these µ-ASOs in colorectal carcinoma cells. The study was conducted using human colorectal adenocarcinoma Caco-2 cells transfected with fully modified µ-ASOs targeting miR-21, miR-17, and miR-155 (oligonucleotides µ-21, µ-17 and µ-155, respectively). The major objectives of the investigation were: 1) to characterize the proteomic signatures induced by each individual µ-ASO, and (2) to assess the integrated proteomic response elicited by combined treatment with all three µ-ASOs. High-resolution proteomic profiling of µ-ASO-treated and control Caco-2 cells, following stringent contaminant filtration, identified 3.957 high-confidence proteins (≥2 unique peptides per protein). Pairwise comparisons between cells treated with control µ-ASO (µ-Scr); single miRNA-targeted µ-ASOs (µ-21, µ-17 and µ-155) or their triple combination (Combi) and control intact Caco-2 cells revealed a list of differentially expressed proteins (DEPs) showing at least a twofold change (log2FC ≥1, p < 0.05), including µ-Scr – 324 DEPs; µ-21 – 663 DEPs; µ-17 – 642 DEPs; µ-155 – 735 DEPs; Combi – 844 DEPs. Functional analysis of the identified DEPs demonstrated that all miRNA-targeted µ-ASOs consistently modulated core metabolic and protein synthesis pathways. In addition, each oligonucleotide also exhibited distinct effects on specific cancer-related processes: µ-21 predominantly influenced apoptosis, cell cycle regulation, proliferation, and DNA repair; µ-17 mainly modulated proliferation and chaperone-related stress responses; and µ-155 primarily affected intracellular transport, apoptotic signaling, and immune response regulation. Notably, the combined µ-ASO treatment produced a distinct, integrative effect—interconnecting these individual pathways into complex regulatory networks that collectively affected a wider spectrum of cellular functions. This work was supported by Russian Scientific Foundation (RSF), grant #19-74-30011
HostingRepository	PRIDE
AnnounceDate	2025-12-05
AnnouncementXML	Submission_2025-12-04_17:29:01.151.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD069826
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Svetlana Miroshnichenko
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-23 06:18:56	ID requested
⏵ 1	2025-12-04 17:29:01	announced

10.3390/IJMS262311747;

10.6019/PXD069826;

submitter keyword: mesyl oligonucleotides, miR-21, antisense oligonucleotides, antimiRs,Colorectal adenocarcinoma, microRNA, miR-17, miR-155, proteomic profiling, Caco-2, LC-MS/MS

Prof Marina A. Zenkova
contact affiliation	Laboratory of nucleic acids biochemistry, Institute of chemical biology and fundamental medicine SB RAS, Russia
contact email	marzen@niboch.nsc.ru
lab head
Svetlana Miroshnichenko
contact affiliation	Institute of chemical biology and fundamental medicine SB RAS
contact email	sveta-mira@yandex.ru
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/2025/12/PXD069826

PRIDE project URI

• PRIDE
  1. PXD069826
     1. Label: PRIDE project
     2. Name: Proteomic profiling of human colorectal adenocarcinoma Caco-2 cells in response to treatment with mesyl oligonucleotides targeting microRNAs miR-21, miR-155, and miR-17