ArticleOncoTargets and therapy2019
Downregulation of miR-21 inhibits the malignant phenotype of pancreatic cancer cells by targeting VHL.
Article in OncoTargets and therapy, 2019. 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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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Aryl Aldehyde-Anchored Small Molecules Recruit FBXO22 for Targeted Degradation of NSD2.Journal of medicinal chemistry · 2026Article
- Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer.Biomedicines · 2026Review
- HypoxamiRs in pancreatic cancer: master regulators of the hypoxic tumor microenvironment.Cell biology and toxicology · 2025Review
- HIF-1α: A Key Factor Mediating Tumor Cells from Digestive System to Evade NK Cell Killing via Activating Metalloproteinases to Hydrolyze MICA/B.Biomolecules · 2025Review
- Molecular roles of microRNA-21 and exosomal miR-21 in gastrointestinal cancers: diagnostic, therapeutic, and drug resistance insights.Frontiers in molecular biosciences · 2025Review
- Recruitment of FBXO22 for targeted degradation of NSD2.Nature chemical biology · 2024Article
- Role of MicroRNA-21 in Prostate Cancer Progression and Metastasis: Molecular Mechanisms to Therapeutic Targets.Annals of surgical oncology · 2024Review
- MicroRNAs: emerging biomarkers and therapeutic targets in pancreatic cancer.Frontiers in molecular biosciences · 2024Review
- The roles of lncRNAs and miRNAs in pancreatic cancer: a focus on cancer development and progression and their roles as potential biomarkers.Frontiers in oncology · 2024Review
- Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer.International journal of molecular sciences · 2023Review
- Overexpression of hypoxia-inducible factor-1α in hidradenitis suppurativa: the link between deviated immunity and metabolism.Archives of dermatological research · 2023Article
- Soft Tissue Ewing Sarcoma Cell Drug Resistance Revisited: A Systems Biology Approach.International journal of environmental research and public health · 2023Article
- VHL tumor suppressor as a novel potential candidate biomarker in papillary thyroid carcinoma.Biomolecules & biomedicine · 2023Review
- LINC02381 suppresses cell proliferation and promotes apoptosis via attenuating IGF1R/PI3K/AKT signaling pathway in breast cancer.Functional & integrative genomics · 2023Article
- Review
- A reciprocal feedback between colon cancer cells and Schwann cells promotes the proliferation and metastasis of colon cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells.International journal of molecular sciences · 2022Article
- Milk Exosomal microRNAs: Postnatal Promoters of β Cell Proliferation but Potential Inducers of β Cell De-Differentiation in Adult Life.International journal of molecular sciences · 2022Review
- microRNA-21-5p from M2 macrophage-derived extracellular vesicles promotes the differentiation and activity of pancreatic cancer stem cells by mediating KLF3.Cell biology and toxicology · 2022Article
- Review of the endocrine organ-like tumor hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMicroRNA (miR)-21 is overexpressed in numerous types of malignancy and participates in the development of cancer. However, the basic mechanism of the influence of miR-21 on the malignant phenotype of pancreatic cancer remains unclear. PURPOSE: The present study aimed to investigate the role of miR-21 in pancreatic cancer development and explore its molecular mechanism. PATIENTS AND
methodsThe tissue samples were collected at the Second Hospital of Tianjin Medical University (Tianjin, China) between January 2013 and December 2015. The expression of VHL in tissue samples was evaluated by IHC staining. The expression of miR-21 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). MiR-21 target gene was detected by real-time PCR, Western blot and the luciferase reporter assay. Cell viability, cell proliferation, cell migration and invasion were evaluated by the MTT assays, the colony formation assays and the transwell assays. The nude mouse tumor xenograft model was performed to detect the effect of miR-21 on tumor growth in vivo.
resultsVon Hippel-Lindau tumor suppressor (VHL) was downregulated in pancreatic cancer tissues compared with pancreatic non-tumor tissues. VHL was identified as a novel direct target of miR-21, by which it is negatively regulated. In PANC-1 cells, inhibition of miR-21 and upregulation of VHL significantly suppressed cell proliferation, migration and invasion. Knockdown of miR-21 inhibited the hypoxia-inducible factor (HIF)-1α/vascular endothelial growth factor (VEGF) pathway, while inhibiting the expression of matrix metallopeptidase (MMP)-2 and MMP-9. Silencing of miR-21 inhibited tumor growth in vivo.
conclusionKnockdown miR-21 increased the expression of VHL, and thus modulated the HIF-1α/VEGF pathway and the expression of MMP-2 and MMP-9, which led to the inhibition of the proliferation, migration and invasion of pancreatic cancer cells. All of these results suggest that the miR-21/VHL interaction may be a novel potential target for pancreatic cancer prevention and therapy.
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