ArticleThe Journal of clinical investigation2014
IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis.
Article in The Journal of clinical investigation, 2014. 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 455 papers.
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Who cites it
455 citing papers in PubMed, 766 citations in OpenAlex.
- IL-6/STAT3 signaling pathway-mediated apoptosis induced by medical ozone water in liver cancer: A mechanistic study.Biomedical reports · 2026Article
- IL-6/STAT3-Mediated miR-181a-5p in Bone Marrow-Derived Mesenchymal Stem Cells Regulates Th17/Treg Balance in Experimental Periodontitis.International dental journal · 2026Article
- In Vitro Antitumor Properties of Simvastatin-Loaded SBA-16 Mesoporous Nanoparticles Using Two- and Three-Dimensional Colorectal Spheroid Models.Pharmaceutics · 2026Article
- Myeloid Mir34a suppresses initiation and progression of intestinal and colitis-induced colon cancers in APCCell death & disease · 2026Article
- THOC3 interacts with epithelial-to-mesenchymal transition to promote non-small cell lung cancer carcinoma progression through STAT3 signaling pathway.Translational oncology · 2026Article
- A Literature Review of Interleukins in the Development and Treatment of Breast Cancer.International journal of molecular sciences · 2026Review
- Extracellular Vesicles fromNanomaterials (Basel, Switzerland) · 2026Article
- The unseen architects of metastasis: coagulation factors in pre-metastatic niche development.Cell communication and signaling : CCS · 2026Review
- Hyperbaric Oxygen Reverses High-Glucose-Induced Stemness and Radioresistance in Non-Small Cell Lung Cancer Cells.Cancer management and research · 2026Article
- Down-regulation of RBM47 due to diminished activation by forkhead box A1 (FOXA1) and silencing by CpG methylation is associated with epithelial-mesenchymal transition and metastasis of colorectal cancer.Molecular biomedicine · 2025Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- CAA-derived IL-6 promoted the PD-L1 expression of breast cancer via STAT3/miR-497a-5p signaling.Journal of cancer research and clinical oncology · 2025Article
- The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications.Non-coding RNA research · 2025Review
- Associations of Biomarkers of Systemic Inflammation, Angiogenesis, and Cell-to-Cell Adhesion With Tumor Budding Among Early-Onset and Later-Onset Colorectal Cancer Patients.Cancer medicine · 2025Observational
- Recent research advances in interleukin, microRNA and neuroendocrine tumor biomarkers (Review).Molecular and clinical oncology · 2025Review
- Molecular interaction of human papilloma virus (HPV) with microRANs: insights into the development of cervical cancer and treatment approaches.Infectious agents and cancer · 2025Review
- Epithelial-mesenchymal transition in colorectal cancer metastasis and progression: molecular mechanisms and therapeutic strategies.Cell death discovery · 2025Review
- Suppression of endometriosis by miRNA-34a via inhibition of matrix metalloproteinase-2: An alternative pathway to impede invasion.Non-coding RNA research · 2025Article
- Inhibition of colorectal carcinogenesis by sunitinib malate: disruption of the IL-6/STAT3/c-MYC/TWIST/MMP2 autocrine signaling axis.Discover oncology · 2025Article
- Exploring miR-301a-3p and osteosarcoma: from expression differences to mechanism of action.Discover oncology · 2025Article
395 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
Members of the miR-34 family are induced by the tumor suppressor p53 and are known to inhibit epithelial-to-mesenchymal transition (EMT) and therefore presumably suppress the early phases of metastasis. Here, we determined that exposure of human colorectal cancer (CRC) cells to the cytokine IL-6 activates the oncogenic STAT3 transcription factor, which directly represses the MIR34A gene via a conserved STAT3-binding site in the first intron. Repression of MIR34A was required for IL-6-induced EMT and invasion. Furthermore, we identified the IL-6 receptor (IL-6R), which mediates IL-6-dependent STAT3 activation, as a conserved, direct miR-34a target. The resulting IL-6R/STAT3/miR-34a feedback loop was present in primary colorectal tumors as well as CRC, breast, and prostate cancer cell lines and associated with a mesenchymal phenotype. An active IL-6R/STAT3/miR-34a loop was necessary for EMT, invasion, and metastasis of CRC cell lines and was associated with nodal and distant metastasis in CRC patient samples. p53 activation in CRC cells interfered with IL-6-induced invasion and migration via miR-34a-dependent downregulation of IL6R expression. In Mir34a-deficient mice, colitis-associated intestinal tumors displayed upregulation of p-STAT3, IL-6R, and SNAIL and progressed to invasive carcinomas, which was not observed in WT animals. Collectively, our data indicate that p53-dependent expression of miR-34a suppresses tumor progression by inhibiting a IL-6R/STAT3/miR-34a feedback loop.
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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.