ArticlePloS one2012
MicroRNAs targeting oncogenes are down-regulated in pancreatic malignant transformation from benign tumors.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Prognostic Role of MicroRNA-126 for Survival in Malignant Tumors: A Systematic Review and Meta-Analysis.Disease markers · 2015Pooled it
- MicroRNA-15a/16 regulate protein metabolism and are associated with clinical outcomes in pancreatic ductal adenocarcinoma.Physiological reports · 2026Article
- Crosstalk between KRAS and miRNAs in pancreatic cancer: Opportunities for its diagnosis, prognosis and therapeutic intervention (Review).International journal of oncology · 2026Review
- Review
- Trials and Tribulations of MicroRNA Therapeutics.International journal of molecular sciences · 2024Review
- Circulating microRNAs as Potential Biomarkers in Pancreatic Cancer-Advances and Challenges.International journal of molecular sciences · 2023Review
- KRAS Hijacks the miRNA Regulatory Pathway in Cancer.Cancer research · 2023Article
- Role of Some microRNA/ADAM Proteins Axes in Gastrointestinal Cancers as a Novel Biomarkers and Potential Therapeutic Targets-A Review.Current issues in molecular biology · 2023Review
- KRAS-related miR-143 expression is associated with lymph node involvement and correlates with outcome in pancreatic adenocarcinoma patients.Frontiers in oncology · 2023Article
- Epigenetic reprogramming in pancreatic premalignancy and clinical implications.Frontiers in oncology · 2023Review
- Article
- Role of microRNAs in response to cadmium chloride in pancreatic ductal adenocarcinoma.Archives of toxicology · 2022Article
- miR-503-5p inhibits colon cancer tumorigenesis, angiogenesis, and lymphangiogenesis by directly downregulating VEGF-A.Gene therapy · 2022Article
- Review of the endocrine organ-like tumor hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma.Frontiers in oncology · 2022Review
- The Role of Circulating MicroRNAs in Patients with Early-Stage Pancreatic Adenocarcinoma.Biomedicines · 2021Review
- Peptidylarginine Deiminase Inhibitor Application, Using Cl-Amidine, PAD2, PAD3 and PAD4 Isozyme-Specific Inhibitors in Pancreatic Cancer Cells, Reveals Roles for PAD2 and PAD3 in Cancer Invasion and Modulation of Extracellular Vesicle Signatures.International journal of molecular sciences · 2021Article
- Association of Genetic Variants Affecting microRNAs and Pancreatic Cancer Risk.Frontiers in genetics · 2021Article
- Bioinformatics Analysis of a Prognostic miRNA Signature and Potential Key Genes in Pancreatic Cancer.Frontiers in oncology · 2021Article
- Article
- Differences between Well-Differentiated Neuroendocrine Tumors and Ductal Adenocarcinomas of the Pancreas Assessed by Multi-Omics Profiling.International journal of molecular sciences · 2020Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMicroRNA (miRNA) expression profiles have been described in pancreatic ductal adenocarcinoma (PDAC), but these have not been compared with pre-malignant pancreatic tumors. We wished to compare the miRNA expression signatures in pancreatic benign cystic tumors (BCT) of low and high malignant potential with PDAC, in order to identify miRNAs deregulated during PDAC development. The mechanistic consequences of miRNA dysregulation were further evaluated.
methodsTissue samples were obtained at a tertiary pancreatic unit from individuals with BCT and PDAC. MiRNA profiling was performed using a custom microarray and results were validated using RT-qPCR prior to evaluation of miRNA targets.
resultsWidespread miRNA down-regulation was observed in PDAC compared to low malignant potential BCT. We show that amongst those miRNAs down-regulated, miR-16, miR-126 and let-7d regulate known PDAC oncogenes (targeting BCL2, CRK and KRAS respectively). Notably, miR-126 also directly targets the KRAS transcript at a "seedless" binding site within its 3'UTR. In clinical specimens, miR-126 was strongly down-regulated in PDAC tissues, with an associated elevation in KRAS and CRK proteins. Furthermore, miR-21, a known oncogenic miRNA in pancreatic and other cancers, was not elevated in PDAC compared to serous microcystic adenoma (SMCA), but in both groups it was up-regulated compared to normal pancreas, implicating early up-regulation during malignant change.
conclusionsExpression profiling revealed 21 miRNAs down-regulated in PDAC compared to SMCA, the most benign lesion that rarely progresses to invasive carcinoma. It appears that miR-21 up-regulation is an early event in the transformation from normal pancreatic tissue. MiRNA expression has the potential to distinguish PDAC from normal pancreas and BCT. Mechanistically the down-regulation of miR-16, miR-126 and let-7d promotes PDAC transformation by post-transcriptional up-regulation of crucial PDAC oncogenes. We show that miR-126 is able to directly target KRAS; re-expression has the potential as a therapeutic strategy against PDAC and other KRAS-driven cancers.
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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.