ArticleMolecular cancer2015
Targeting STAT3/miR-21 axis inhibits epithelial-mesenchymal transition via regulating CDK5 in head and neck squamous cell carcinoma.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- A PRISMA meta-analysis for diagnostic value of microRNA-21 in head and neck squamous cell carcinoma along with bioinformatics research.Oral and maxillofacial surgery · 2024Pooled it
- Neupogen/MSCs conditioned media inhibit HEp-2 laryngeal cancer cells proliferation by down regulating miRNA 21expression and ROS production.Molecular biology reports · 2026Article
- Comprehensive exploration of programmed cell death landscape in lung adenocarcinoma combining multi-omic analysis and experimental verification.Scientific reports · 2025Article
- Adeno-associated virus mediated artificial circular RNA for triggering cancer immunotherapy to treat prostate cancer.Frontiers in oncology · 2025Article
- Saliva in Balancing Oral and Systemic Health, Oral Cancer, and Beyond: A Narrative Review.Cancers · 2024Review
- Role of microRNAs in triple‑negative breast cancer and new therapeutic concepts (Review).Oncology letters · 2024Review
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- Marine-Derived Compounds for CDK5 Inhibition in Cancer: Integrating Multi-Stage Virtual Screening, MM/GBSA Analysis and Molecular Dynamics Investigations.Metabolites · 2023Article
- Acetyl-cinobufagin suppresses triple-negative breast cancer progression by inhibiting the STAT3 pathway.Aging · 2023Article
- A Comprehensive Review of Natural Products as Therapeutic or Chemopreventive Agents against Head and Neck Squamous Cell Carcinoma Cells Using Preclinical Models.Biomedicines · 2023Review
- Sulforaphane-Induced Cell Mitotic Delay and Inhibited Cell Proliferation via Regulating CDK5R1 Upregulation in Breast Cancer Cell Lines.Biomedicines · 2023Article
- MicroRNA31 and MMP-1 contribute to the differentiated pathway of invasion -with enhanced epithelial-to-mesenchymal transition- in squamous cell carcinoma of the skin.Archives of dermatological research · 2022Article
- STAT3 pathway in cancers: Past, present, and future.MedComm · 2022Review
- Article
- Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data.Bioscience reports · 2021Article
- Cinobufagin suppresses colorectal cancer growth via STAT3 pathway inhibition.American journal of cancer research · 2021Article
- Influence of CDK5 Regulatory Subunit-Associated Protein 1-Like 1 Expression on the Survival of Patients with Non-Metastatic Nasopharyngeal Carcinoma.Cancer management and research · 2021Article
- Review
- Regulation of JAK/STAT signal pathway by miR-21 in the pathogenesis of juvenile idiopathic arthritis.World journal of pediatrics : WJP · 2020Article
- MicroRNAs: potential biomarkers for diagnosis and prognosis of different cancers.Translational cancer research · 2020Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAbnormal activation of STAT3 and miR-21 plays a vital role in progression and invasion of solid tumors. The cyclin-dependent kinase 5 (CDK5) is reported to contribute to cancer metastasis by regulating epithelial-mesenchymal transition (EMT). However, the role of STAT3/miR-21 axis and CDK5 in head and neck squamous cell carcinoma remains unclear.
methodsWe measured the expression of miR-21, CDK5 and EMT markers in 60 HNSCC tumor samples. We used Immunohistochemistry and in situ hybridization assay to examine the role of STAT3/miR-21 axis and CDK5 activation in the invasiveness of HNSCC. The clinical survival relevance was analyzed by Kaplan-Meier analysis and univariate/multivariate COX regression model. Multiple approaches including scratch, transwell chamber assay and other molecular biology techniques were used to validate the anti-invasion effect of targeting miR-21 in Tca8113 and Hep-2 cell lines in vitro. Furthermore, whether miR-21 depletion inhibits HNSCC invasion in vivo was confirmed in Tca8113 xenograft tumor model.
resultsThe expression of miR-21 and CDK5 were significantly correlated with lymph node metastasis in HNSCC. Hep-2 and Tca8113 cell lines showed co-overexpression of miR-21 and CDK5. WP1066 or asON-miR-21 treatment depleted miR-21 and CDK5 expression and significantly inhibited migration or invasion in Hep-2 and Tca8113 cells. The expression levels of CDK5/p35, N-cadherin, vimentin, β-catenin were inhibited while E-cadherin level was increased by miR-21 depletion in vitro and in vivo. Conversely, ectopic CDK5 overexpression significantly induced tumor cell motility and EMT. Moreover, ectopic CDK5 overexpression in Hep-2 and Tca8113 cells rescued the observed phenotype after miR-21 silencing or WP1066 treatment.
conclusionsmiR-21 cooperates with CDK5 to promote EMT and invasion in HNSCC. This finding suggests that CDK5 may be an important cofactor for targeting when designing metastasis-blocking therapy by targeting STAT3/miR-21 axis with STAT3 inhibitor or miR-21 antisense oligonucleotide. This is the first demonstration of the novel role of STAT3/miR-21 axis and CDK5/CDK5R1 (p35) in metastasis of HNSCC.
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