ArticleJournal of translational medicine2025
The integrative genomic and functional immunological analyses of colorectal cancer initiating cells to modulate stemness properties and the susceptibility to immune responses.
Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
7 citing papers in PubMed.
- Review
- Chemoradiotherapy facilitates siglec-10Cancer immunology, immunotherapy : CII · 2026Article
- Expression profiling of inhibitory immune checkpoints in colorectal cancer stem cells and their association with tumor immunity and immunotherapy biomarkers.Frontiers in immunology · 2026Article
- Comparative proteomic analysis of colorectal cancer stem cells reveals potential biomarkers and altered pathways.Frontiers in molecular biosciences · 2026Article
- The Role of Natural Chalcones and Their Derivatives in Targeting Prostate Cancer: Recent Updates.International journal of molecular sciences · 2025Review
- The role of immune checkpoints in modulating cancer stem cells anti-tumor immune responses: implications and perspectives in cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors.
Funding
Abstract
backgroundColorectal cancer (CRC) initiating cells (CICs) possess self-renewal capabilities and are pivotal in tumor recurrence and resistance to conventional therapies, including immunotherapy. The mechanisms underlying their interaction with immune cells remain unclear.
methodsWe conducted a multi-omics analysis-encompassing DNA methylation, total RNA sequencing, and microRNAs (miRNAs; N = 800) profiling on primary CICs and differentiated tumor cell lines, including autologous pairs. Functional immunological assays were performed to assess the impact of miRNA modulation.
resultsCICs exhibited distinct methylation patterns, transcriptomic profiles, and miRNA expressions compared to differentiated tumor cells (p < 0.05 or 0.01). Notably, miRNA-15a and -196a were implicated in regulating tumorigenic pathways, such as epithelial-to-mesenchymal transition (EMT), TGF-β signaling, and immune modulation. The transfection of CICs with miRNA mimics led to the downregulation of oncogenic EMT markers (CRKL, lncRNA SOX2-OT, JUNB, SMAD3) and TGF-β pathway, resulting in a significant reduction of the in vitro proliferation and the tumorigenicity and migration in a zebrafish xenograft model. Additionally, miRNA-15a enhanced the expression of antigen processing machinery and decreased the expression of immune checkpoints (PD-L1, PD-L2, CTLA-4) and immunosuppressive cytokines (IL-4). The co-culture of HLA-matched lymphocytes with CICs overexpressing the miRNA-15a, elicited robust tumor-specific immune responses, characterized by a shift toward central and effector memory T cell phenotypes and prevented their terminal differentiation and exhaustion. The combination of miRNA modulation with Indoleamine 2,3-dioxygenase blockade and immunomodulating agents further potentiated these effects.
conclusionsOur study demonstrates that the modulation of miRNA-15a in CICs not only suppresses the tumorigenic properties but also enhances their visibility to the immune system by upregulating antigen presentation and reducing immunomodulatory molecules. These findings suggest that combining miRNA modulation with epigenetic or immunomodulatory agents holds significant promise for overcoming treatment resistance in CRC.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.