ArticleProceedings of the National Academy of Sciences of the United States of America2015
The CDX1-microRNA-215 axis regulates colorectal cancer stem cell differentiation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Pooled it
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications.Non-coding RNA research · 2025Review
- Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.Frontiers in cell and developmental biology · 2025Review
- (Sialyl)Lewis Antigen Expression on Glycosphingolipids, N-, and O-Glycans in Colorectal Cancer Cell Lines is Linked to a Colon-Like Differentiation Program.Molecular & cellular proteomics : MCP · 2024Article
- A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.Human molecular genetics · 2024Article
- In-Depth Analysis of theInternational journal of molecular sciences · 2023Article
- A Group of Tumor-Suppressive micro-RNAs Changes Expression Coordinately in Colon Cancer.Current issues in molecular biology · 2023Article
- Small Non-Coding RNAs in Human Cancer.Genes · 2022Review
- miR-374a-5p regulates inflammatory genes and monocyte function in patients with inflammatory bowel disease.The Journal of experimental medicine · 2022Article
- miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by TargetingInternational journal of molecular sciences · 2022Article
- Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome.International journal of molecular sciences · 2021Review
- The Cellular Prion Protein: A Promising Therapeutic Target for Cancer.International journal of molecular sciences · 2020Review
- Article
- The effect of miRNA and autophagy on colorectal cancer.Cell proliferation · 2020Review
- miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation.International journal of molecular sciences · 2020Review
- Review
- Indium-111-labeled CD166-targeted peptide as a potential nuclear imaging agent for detecting colorectal cancer stem-like cells in a xenograft mouse model.EJNMMI research · 2020Article
- Deregulation of cancer-stem-cell-associated miRNAs in tissues and sera of colorectal cancer patients.Oncotarget · 2020Article
- PERK-mediated induction of microRNA-483 disrupts cellular ATP homeostasis during the unfolded protein response.The Journal of biological chemistry · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The transcription factor caudal-type homeobox 1 (CDX1) is a key regulator of differentiation in the normal colon and in colorectal cancer (CRC). CDX1 activates the expression of enterocyte genes, but it is not clear how the concomitant silencing of stem cell genes is achieved. MicroRNAs (miRNAs) are important mediators of gene repression and have been implicated in tumor suppression and carcinogenesis, but the roles of miRNAs in differentiation, particularly in CRC, remain poorly understood. Here, we identified microRNA-215 (miR-215) as a direct transcriptional target of CDX1 by using high-throughput small RNA sequencing to profile miRNA expression in two pairs of CRC cell lines: CDX1-low HCT116 and HCT116 with stable CDX1 overexpression, and CDX1-high LS174T and LS174T with stable CDX1 knockdown. Validation of candidate miRNAs identified by RNA-seq in a larger cell-line panel revealed miR-215 to be most significantly correlated with CDX1 expression. Quantitative ChIP-PCR and promoter luciferase assays confirmed that CDX1 directly activates miR-215 transcription. miR-215 expression is depleted in FACS-enriched cancer stem cells compared with unsorted samples. Overexpression of miR-215 in poorly differentiated cell lines causes a decrease in clonogenicity, whereas miR-215 knockdown increases clonogenicity and impairs differentiation in CDX1-high cell lines. We identified the genome-wide targets of miR-215 and found that miR-215 mediates the repression of cell cycle and stemness genes downstream of CDX1. In particular, the miR-215 target gene BMI1 has been shown to promote stemness and self-renewal and to vary inversely with CDX1. Our work situates miR-215 as a link between CDX1 expression and BMI1 repression that governs differentiation in CRC.
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Registered trials
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