ArticleFrontiers in oncology2019
miR-4666-3p and miR-329 Synergistically Suppress the Stemness of Colorectal Cancer Cells via Targeting TGF-β/Smad Pathway.
Article in Frontiers in oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- MicroRNAs Play Key Roles in Progenitor Maintenance, Proliferation, and Osteogenic Differentiation of Osteogenic Progenitor Cells in Syndromic and Nonsyndromic Craniosynostosis.International journal of molecular sciences · 2026Article
- Tumor-Suppressive microRNA Therapy Inhibits Growth of Glioblastoma Multiforme Xenografts.Cancers · 2026Article
- Mendelian randomization and mediation analysis reveal the role of immune cells in the pathways between inflammatory factors and glioblastoma.The Journal of international medical research · 2025Article
- Review
- Discovery and Validation of Novel microRNA Panel for Non-Invasive Prediction of Prostate Cancer.Cureus · 2024Article
- Article
- A concise review on miRNAs as regulators of colon cancer stem cells and associated signalling pathways.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers.Biomolecules · 2023Review
- Signaling pathways and therapeutic interventions in gastric cancer.Signal transduction and targeted therapy · 2022Review
- Regulatory RNAs, microRNA, long-non coding RNA and circular RNA roles in colorectal cancer stem cells.World journal of gastrointestinal oncology · 2022Review
- Ischemic Preconditioning Modulates the Peripheral Innate Immune System to Promote Anti-Inflammatory and Protective Responses in Mice Subjected to Focal Cerebral Ischemia.Frontiers in immunology · 2022Article
- Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells.Cancer communications (London, England) · 2021Review
- Curcumin inhibits prostate cancer progression by regulating the miR-30a-5p/PCLAF axis.Experimental and therapeutic medicine · 2021Article
- MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Epigenetic Signaling of Cancer Stem Cells During Inflammation.Frontiers in cell and developmental biology · 2021Review
- Strategies for Targeting Gene Therapy in Cancer Cells With Tumor-Specific Promoters.Frontiers in oncology · 2020Review
- TRIM37 Mediates Chemoresistance and Maintenance of Stemness in Pancreatic Cancer CellsFrontiers in oncology · 2020Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quiescent caner stem cells are identified as a subpopulation of colon cancer cells in dormant state and possess strong stem-cell like characteristics. Previously, we have identified this subpopulation in colorectal cancer (quiescent colon cancer stem cells, QCCSCs), and find QCCSCs are sensitive to the apoptotic effect of IFN-γ, which is attributed to their high IFN-γR expression levels. Microarray and bioinformatic analysis indicate miR-4666-3p is low expressed in QCCSCs and target IFN-γR1/2, which is proved by luciferase assay and western-blot. Furthermore, we find miR-4666-3p could also target TGF-βR1 to block the activation of TGF-β1/Smad pathway, therefore function as a tumor suppressor gene to inhibit the stemness of colon cancer cells. Besides, compared with QCCSCs, we find the TGF-β1 expression also decreased with the weakening of stemness properties. In terms of mechanism, our result reveal TGF-β1 is the target gene of miR-329, which is also high expressed in non-QCCSCs. Thereafter, we perform gain- and loss- function experiments to confirm the synergistic effect between miR-4666-3p and miR-329 in blocking the activation of TGF-β/Smad pathway. Finally, we evaluate the expression of both miR-4666-3p and miR-329 in 73 tumor specimens and paired normal tissue, and find both two miRNAs are related to unfavorable prognosis and advanced tumor stage in colorectal cancer. Our study revealed a novel epigenetic regulation mechanism in colon cancer stem cells, which could be exploited as a novel therapeutic strategy for cancer treatment.
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