ArticleScientific reports2017
Microenvironment regulates the expression of miR-21 and tumor suppressor genes PTEN, PIAS3 and PDCD4 through ZAP-70 in chronic lymphocytic leukemia.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Phosphatases of regenerating liver downregulate PTEN to promote tumorigenesis.Biochemical Society transactions · 2026Review
- Prevalence and risk factors of metabolic syndrome in survivors of childhood acute leukemia: a systematic review and meta-analysis.Diabetology & metabolic syndrome · 2026Review
- PDCD4: A critical regulator in leukemic signaling networks and its therapeutic potential.Molecular biology reports · 2025Review
- IGF1R-targeted delivery of a bridged nucleic acid oligonucleotide-peptide conjugate for microRNA-21 inhibition in triple-negative breast cancer.NAR cancer · 2025Article
- The crosstalk between MiRNAs and autophagy in leukemia: mechanisms and therapeutic insights.Discover oncology · 2025Review
- Article
- Pre-analytical considerations for microRNA quantification in childhood leukemia research.Journal of biological methods · 2025Review
- Knockdown of AMIGO2 suppresses proliferation and migration through regulating PPAR-γ in bladder cancer.Hereditas · 2024Article
- PIAS family in cancer: from basic mechanisms to clinical applications.Frontiers in oncology · 2024Review
- DEX-Induced SREBF1 Promotes BMSCs Differentiation into Adipocytes to Attract and Protect Residual T-Cell Acute Lymphoblastic Leukemia Cells After Chemotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Simultaneous Targeting of Multiple oncomiRs with Phosphorothioate or PNA-Based Anti-miRs in Lymphoma Cell Lines.Pharmaceutical research · 2022Article
- MicroRNAs and JAK/STAT3 signaling: A new promising therapeutic axis in blood cancers.Genes & diseases · 2022Review
- Article
- Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Non-Coding RNAs as Cancer Hallmarks in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2020Review
- Small RNAs, Big Diseases.International journal of molecular sciences · 2020Review
- Review
- Stat-3 signaling promotes cell proliferation and metastasis of gastric cancer through PDCD4 downregulation.The Kaohsiung journal of medical sciences · 2020Article
- Targeted inhibition of mRNA translation initiation factors as a novel therapeutic strategy for mature B-cell neoplasms.Exploration of targeted anti-tumor therapy · 2020Article
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic lymphocytic leukemia (CLL) cells are highly dependent on microenvironment, being the BCR pathway one key player in this crosstalk. Among proteins participating, ZAP-70 enhances response to microenvironmental stimuli. MicroRNA-21 (miR-21) is overexpressed in diverse neoplasias including CLL, where it has been associated to refractoriness to fludarabine and to shorter time to progression and survival. To further elucidate the role of ZAP-70 in the biology of CLL, we studied its involvement in miR-21 regulation. MiR-21 expression was higher in CLL cells with high ZAP-70. Ectopic expression of ZAP-70 induced transcription of miR-21 via MAPK and STAT3, which subsequently induced downregulation of tumor suppressors targeted by miR-21. The co-culture of primary CLL cells mimicking the microenvironment induced ZAP-70 and miR-21 expression, as well as downregulation of miR-21 targets. Interestingly, the increase in miR-21 after co-culture was significantly impaired by ibrutinib, indicating that the BCR signaling pathway is involved in its regulation. Finally, survival of CLL cells induced by the co-culture correlated with miR-21 upregulation. In conclusion, stimuli from the microenvironment regulate miR-21 and its targeted tumor suppressor genes via a signaling pathway involving ZAP-70, thus contributing to the cytoprotection offered by the microenvironment particularly observed in CLL cells expressing ZAP-70.
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