ArticlePloS one2013
MicroRNA-224 targets SMAD family member 4 to promote cell proliferation and negatively influence patient survival.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- Plant-Derived Secondary Metabolites Modulating Inflammation-Driven Pathways in Hepatocellular Carcinoma: Preclinical Insights.Current issues in molecular biology · 2026Review
- Anti-senescence Effects of Nanovesicles Derived from Cluster of Differentiation-146-Positive Tonsil Mesenchymal Stem Cells via Modulation of the Tumor Protein 53 Pathway.Biomaterials research · 2026Article
- MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?Cancers · 2023Review
- Different types of bisphenols alter ovarian steroidogenesis: Special attention to BPA.Heliyon · 2023Article
- Maintenance of gut barrier integrity after injury: Trust your gut microRNAs.Journal of leukocyte biology · 2021Review
- miR-224 Regulates the Aggressiveness of Hepatoma Cells Through the IL-6/STAT3/SMAD4 Pathway.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2021Article
- Long Non-Coding RNA TRG-AS1 Promoted Proliferation and Invasion of Lung Cancer Cells Through the miR-224-5p/SMAD4 Axis.OncoTargets and therapy · 2021Article
- Review
- Unique microRNA alterations in hepatocellular carcinomas arising either spontaneously or due to chronic exposure to Ginkgo biloba extract (GBE) in B6C3F1/N mice.Archives of toxicology · 2020Article
- MicroRNAs in Animal Models of HCC.Cancers · 2019Review
- MicroRNA Expression in Focal Nodular Hyperplasia in Comparison with Cirrhosis and Hepatocellular Carcinoma.Pathology oncology research : POR · 2019Article
- miR-224 Is Significantly Upregulated and Targets Caspase-3 and Caspase-7 During Colorectal Carcinogenesis.Translational oncology · 2019Article
- MicroRNA-224 Promotes Tumorigenesis through Downregulation of Caspase-9 in Triple-Negative Breast Cancer.Disease markers · 2019Article
- Cancer Metabolism as a Mechanism of Treatment Resistance and Potential Therapeutic Target in Hepatocellular Carcinoma.Yonsei medical journal · 2018Review
- Prospects of Noncoding RNAs in Hepatocellular Carcinoma.BioMed research international · 2018Review
- Association of miR-146 rs2910164, miR-196a rs11614913, miR-221 rs113054794 and miR-224 rs188519172 polymorphisms with anti-TNF treatment response in a Greek population with Crohn's disease.World journal of gastrointestinal pharmacology and therapeutics · 2017Article
- Downregulated USP3 mRNA functions as a competitive endogenous RNA of SMAD4 by sponging miR-224 and promotes metastasis in colorectal cancer.Scientific reports · 2017Article
- Review
- MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway.Scientific reports · 2017Article
- miR-224 Controls Human Colorectal Cancer Cell Line HCT116 Proliferation by Targeting Smad4.International journal of medical sciences · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNA-224 (miR-224) is frequently over-expressed in liver and colorectal cancers. We and others have previously described the role of miR-224 over-expression in cell proliferation in vitro but we have yet to identify the relevant miR-224 direct target. In this study, we further demonstrated that miR-224 up-regulation promotes cell proliferation using both in vitro assays and in vivo tumor growth models. We systematically screened for high confidence miR-224 targets by overlapping in silico predicted targets from multiple algorithms and significantly down-regulated genes in miR-224-expressing cells from whole genome expression microarrays. A total of 72 high confidence miR-224 targets were identified and found to be enriched in various cancer-related processes. SMAD family member 4 (SMAD4) is experimentally validated as the direct cellular target through which miR-224 promotes cell proliferation. The clinical relevance of our experimental observations was supported by a statistically significant inverse correlation between miR-224 and SMAD4 transcript expression in tumor versus paired adjacent non-tumorous tissues from HCC patients (p<0.001, r= -0.45, R(2) =0.122). Furthermore, miR-224 up-regulation and SMAD4 down-regulation is significantly associated with poorer patient survival (p<0.05). In summary, miR-224/SMAD4 pathway is a clinically relevant pathway to provide new insights in understanding HCC. (191 words).
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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.