ArticleCellular and molecular gastroenterology and hepatology2020
Characterization of a p53/miR-34a/CSF1R/STAT3 Feedback Loop in Colorectal Cancer.
Article in Cellular and molecular gastroenterology and hepatology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 106 citations in OpenAlex.
- Myeloid Mir34a suppresses initiation and progression of intestinal and colitis-induced colon cancers in APCCell death & disease · 2026Article
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- Visceral and subcutaneous adipose stem cells modulate colorectal cancer cell progression: direct and indirect contact distinctly accelerate tumor aggressiveness.Molecular medicine (Cambridge, Mass.) · 2026Article
- MiR-34a deficiency enhances nucleic acid sensing and type I IFN signaling in a mouse model of Alzheimer's disease.Frontiers in immunology · 2026Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Myeloid Mir34a suppresses colitis-associated colon cancer: characterization of mediators by single-cell RNA sequencing.Cell death and differentiation · 2025Article
- MiRNAs as major players in brain health and disease: current knowledge and future perspectives.Cell death discovery · 2025Review
- Liver-derived Exosomal miRNA in NAFLD: Mechanisms of Action, Biomarkers, and Therapeutic Applications.Current medicinal chemistry · 2025Review
- Role of FHOD1 in tumor cells and tumor immune microenvironment.Frontiers in immunology · 2025Review
- Epigenetically Regulating Non-coding RNAs in Colorectal Cancer: Promises and Potentials.Middle East journal of digestive diseases · 2025Review
- The role of intestinal macrophage polarization in colitis-associated colon cancer.Frontiers in immunology · 2025Review
- Role of the p53/miR-34a/SIRT1 Feedback Loop in Metformin-induced Radiosensitivity of Colorectal Cancer Cells.Current radiopharmaceuticals · 2025Article
- Insights into CSF-1R Expression in the Tumor Microenvironment.Biomedicines · 2024Review
- Role of extracellular vesicles associated with microRNAs and their interplay with cuproptosis in osteoporosis.Non-coding RNA research · 2024Review
- Targeting CSF1R in myeloid-derived suppressor cells: insights into its immunomodulatory functions in colorectal cancer and therapeutic implications.Journal of nanobiotechnology · 2024Article
- Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors.Bioactive materials · 2024Review
- MicroRNA-34 and gastrointestinal cancers: a player with big functions.Cancer cell international · 2024Review
- JAK/STAT in leukemia: a clinical update.Molecular cancer · 2024Review
- TP53 to mediate immune escape in tumor microenvironment: an overview of the research progress.Molecular biology reports · 2024Review
- CSF-1R in Cancer: More than a Myeloid Cell Receptor.Cancers · 2024Review
Corrections and comments
- Erratum issuedCorrection.2026
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsThe miR-34a gene is a direct target of p53 and is commonly silenced in colorectal cancer (CRC). Here we identified the receptor tyrosine kinase CSF1R as a direct miR-34a target and characterized CSF1R as an effector of p53/miR-34a-mediated CRC suppression.
methodsAnalyses of TCGA-COAD and three other CRC cohorts for association of mRNA expression and signatures with patient survival and molecular subtypes. Bioinformatics identification and experimental validation of miRNA and transcription factor targets. Functional analysis of factors/pathways in the regulation of epithelial-mesenchymal transition (EMT), invasion, migration, acquired chemo-resistance and metastasis. Analyses of protein expression and CpG methylation within primary human colon cancer samples.
resultsIn primary CRCs increased CSF1R, CSF1 and IL34 expression was associated with poor patient survival and a mesenchymal-like subtype. CSF1R displayed an inverse correlation with miR-34a expression. This was explained by direct inhibition of CSF1R by miR-34a. Furthermore, p53 repressed CSF1R via inducing miR-34a, whereas SNAIL induced CSF1R both directly and indirectly via repressing miR-34a in a coherent feed-forward loop. Activation of CSF1R induced EMT, migration, invasion and metastasis of CRC cells via STAT3-mediated down-regulation of miR-34a. 5-FU resistance of CRC cells was mediated by CpG-methylation of miR-34a and the resulting elevated expression of CSF1R. In primary CRCs elevated expression of CSF1R was detected at the tumor invasion front and was associated with CpG methylation of the miR-34a promoter as well as distant metastasis.
conclusionsThe reciprocal inhibition between miR-34a and CSF1R and its loss in tumor cells may be relevant for therapeutic and prognostic approaches towards CRC management.
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