ArticleCarcinogenesis2012
MiRNA-335 suppresses neuroblastoma cell invasiveness by direct targeting of multiple genes from the non-canonical TGF-β signalling pathway.
Article in Carcinogenesis, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 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.
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Who cites it
95 citing papers in PubMed, 150 citations in OpenAlex.
- Role of SFTPD/miR-335-5p/lnc-HNRNPUL2 axis in colorectal cancer: in silico characterization and clinical validation.BMC cancer · 2026Article
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Regulation and dysregulation of microRNA - transcription factor axes in differentiation and neuroblastoma.Cellular and molecular life sciences : CMLS · 2025Review
- Combination of clinical parameters andQuantitative imaging in medicine and surgery · 2025Article
- LRG1 Contributes to the Pathogenesis of Multiple Kidney Diseases: A Comprehensive Review.Kidney diseases (Basel, Switzerland) · 2024Review
- A multi-omics approach for biomarker discovery in neuroblastoma: a network-based framework.NPJ systems biology and applications · 2024Article
- Increased level of serum leucine-rich-alpha-2-glycoprotein 1 in patients with clear cell renal cell carcinoma.BMC urology · 2024Article
- Case report: Cytokine and miRNA profiling in multisystem inflammatory syndrome in children.Frontiers in medicine · 2024Article
- Epigenetic Dysregulation inInternational journal of molecular sciences · 2023Review
- Review
- Drugging Hijacked Kinase Pathways in Pediatric Oncology: Opportunities and Current Scenario.Pharmaceutics · 2023Review
- LRG-1 promotes fat graft survival through the RAB31-mediated inhibition of hypoxia-induced apoptosis.Journal of cellular and molecular medicine · 2022Article
- LRG1 mediated by ATF3 promotes growth and angiogenesis of gastric cancer by regulating the SRC/STAT3/VEGFA pathway.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- The role of ncRNAs in neuroblastoma: mechanisms, biomarkers and therapeutic targets.Biomarker research · 2022Review
- LRG1: an emerging player in disease pathogenesis.Journal of biomedical science · 2022Review
- LRG1 promotes hypoxia-induced cardiomyocyte apoptosis and autophagy by regulating hypoxia-inducible factor-1α.Bioengineered · 2021Article
- MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021Review
- Blood small extracellular vesicles derived miRNAs to differentiate pancreatic ductal adenocarcinoma from chronic pancreatitis.Clinical and translational medicine · 2021Article
- Non-coding RNAs in Wilms' tumor: biological function, mechanism, and clinical implications.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Transforming growth factor-β (TGF-β) signaling regulates many diverse cellular activities through both canonical (SMAD-dependent) and non-canonical branches, which includes the mitogen-activated protein kinase (MAPK), Rho-like guanosine triphosphatase and phosphatidylinositol-3-kinase/AKT pathways. Here, we demonstrate that miR-335 directly targets and downregulates genes in the TGF-β non-canonical pathways, including the Rho-associated coiled-coil containing protein (ROCK1) and MAPK1, resulting in reduced phosphorylation of downstream pathway members. Specifically, inhibition of ROCK1 and MAPK1 reduces phosphorylation levels of the motor protein myosin light chain (MLC) leading to a significant inhibition of the invasive and migratory potential of neuroblastoma cells. Additionally, miR-335 targets the leucine-rich alpha-2-glycoprotein 1 (LRG1) messenger RNA, which similarly results in a significant reduction in the phosphorylation status of MLC and a decrease in neuroblastoma cell migration and invasion. Thus, we link LRG1 to the migratory machinery of the cell, altering its activity presumably by exerting its effect within the non-canonical TGF-β pathway. Moreover, we demonstrate that the MYCN transcription factor, whose coding sequence is highly amplified in a particularly clinically aggressive neuroblastoma tumor subtype, directly binds to a region immediately upstream of the miR-335 transcriptional start site, resulting in transcriptional repression. We conclude that MYCN contributes to neuroblastoma cell migration and invasion, by directly downregulating miR-335, resulting in the upregulation of the TGF-β signaling pathway members ROCK1, MAPK1 and putative member LRG1, which positively promote this process. Our results provide novel insight into the direct regulation of TGF-β non-canonical signaling by miR-335, which in turn is downregulated by MYCN.
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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.