ArticleCell death & disease2015
Autoregulatory loop between TGF-β1/miR-411-5p/SPRY4 and MAPK pathway in rhabdomyosarcoma modulates proliferation and differentiation.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 36 citations in OpenAlex.
- Multi-Omics Analysis Reveals m7G Methylation-Related Genes May Be Involved in TGF-β Signaling-Mediated Anti-PD-L1 Response in Bladder Cancer.ImmunoTargets and therapy · 2026Article
- Expression profiles of miR-411 and SPRY4 as indicators of disease progression and treatment in chronic myelogenous leukemia.Scientific reports · 2025Article
- Integrative bioinformatics analysis and experimental validation identify CHEK1 as an unfavorable prognostic biomarker related to immunosuppressive phenotypes in soft tissue sarcomas.NPJ precision oncology · 2025Article
- Role of SPRY4 in health and disease.Frontiers in oncology · 2024Review
- Sprouty4 is epigenetically upregulated in human colorectal cancer.Epigenetics · 2023Article
- MicroRNA-Mediated Regulation of Histone-Modifying Enzymes in Cancer: Mechanisms and Therapeutic Implications.Biomolecules · 2023Review
- MicroRNAs in the Pathogenesis, Prognostication and Prediction of Treatment Resistance in Soft Tissue Sarcomas.Cancers · 2023Review
- A GRIP-1-EZH2 switch binding to GATA-4 is linked to the genesis of rhabdomyosarcoma through miR-29a.Oncogene · 2022Article
- Article
- High-Metastatic Melanoma Cells Promote the Metastatic Capability of Low-Metastatic Melanoma CellsFrontiers in oncology · 2022Article
- A Novel Prognostic Risk Model for Cervical Cancer Based on Immune Checkpoint HLA-G-Driven Differentially Expressed Genes.Frontiers in immunology · 2022Article
- HIF-1α-activated long non-coding RNA KDM4A-AS1 promotes hepatocellular carcinoma progression via the miR-411-5p/KPNA2/AKT pathway.Cell death & disease · 2021Article
- Enhancement of myogenic differentiation and inhibition of rhabdomyosarcoma progression by miR-28-3p and miR-193a-5p regulated by SNAIL.Molecular therapy. Nucleic acids · 2021Article
- Long-Lasting Activity of ERK Kinase Depends on NFATc1 Induction and Is Involved in Cell Migration-Fusion in Murine Macrophages RAW264.7.International journal of molecular sciences · 2020Article
- hsa-microRNA-411-5p regulates proliferation, migration and invasion by targeting the hyaluronan mediated motility receptor in ovarian cancer.Experimental and therapeutic medicine · 2020Article
- MicroRNA-29 family inhibits rhabdomyosarcoma formation and progression by regulating GEFT function.American journal of translational research · 2020Article
- Up-regulation of circ_0000353 impedes the proliferation and metastasis of non-small cell lung cancer cells via adsorbing miR-411-5p and increasing forkhead box O1.Cancer biomarkers : section A of Disease markers · 2020Article
- Prognostic and predictive roles of microRNA‑411 and its target STK17A in evaluating radiotherapy efficacy and their effects on cell migration and invasion via the p53 signaling pathway in cervical cancer.Molecular medicine reports · 2020Article
- miRNA signatures in childhood sarcomas and their clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019Review
- Oncogenic microRNA-411 promotes lung carcinogenesis by directly targeting suppressor genes SPRY4 and TXNIP.Oncogene · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The origin of rhabdomyosarcoma (RMS) remains controversial. However, specific microRNAs (miRNAs) are downregulated in RMS and it is possible that re-expression of these miRNAs may lead to differentiation. Transforming growth factor-β1 (TGF-β1) is known to block differentiation of RMS. We therefore analyzed miRNA microarrays of RMS cell lines with or without TGF-β1 knockdown and identified a novel anti-oncogene miR-411-5p. Re-expression of miR-411-5p inhibited RMS cell proliferation in vitro and tumorigenicity in vivo. Using a luciferase reporting system and sequence analysis, the potential target of miR-411-5p was identified as sprouty homolog 4 (SPRY4), which inhibits protein kinase Cα-mediated activation of mitogen-activated protein kinases (MAPKs), especially p38MAPK phosphorylation. These results revealed an inverse correlation between TGF-β1/SPRY4 and miR-411-5p levels. SPRY4 small interfering RNA and miR-411-5p both activated p38MAPK phosphorylation and also promoted apoptosis and myogenic differentiation, indicated by increased caspase-3, myosin heavy chain, and myosin expression. SPRY4 and miR-411 mRNA levels correlated with TGF-β1 expression levels in RMS tissues, which was confirmed by immunohistochemical staining for TGF-β1, SPRY4, and phosphorylated p38MAPK proteins. Overall, these results indicate that miR-411-5p acts as an RMS differentiation-inducing miRNA prompting p38MAPK activation via directly downregulating SPRY4. These results establish an autoregulatory loop between TGF-β1/miR-411-5p/SPRY4 and MAPK in RMS, which governs the switch between proliferation and differentiation.
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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.