ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
Nrf2-miR-129-3p-mTOR Axis Controls an miRNA Regulatory Network Involved in HDACi-Induced Autophagy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Pexophagy and Oxidative Stress: Focus on Peroxisomal Proteins and Reactive Oxygen Species (ROS) Signaling Pathways.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson's Disease with Potential Therapeutic Implications.Biomolecules · 2025Review
- Advances of HDAC inhibitors in tumor therapy: potential applications through immune modulation.Frontiers in oncology · 2025Review
- miR-129 Regulates Yak Intramuscular Preadipocyte Proliferation and Differentiation through the PI3K/AKT Pathway.International journal of molecular sciences · 2024Article
- Dimethyl Fumarate and Intestine: From Main Suspect to Potential Ally against Gut Disorders.International journal of molecular sciences · 2023Review
- Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials.Molecules (Basel, Switzerland) · 2023Review
- Regulatory miRNAs in cancer cell recovery from therapy exposure and its implications as a novel therapeutic strategy for preventing disease recurrence.The Enzymes · 2023Article
- An update on the bridging factors connecting autophagy and Nrf2 antioxidant pathway.Frontiers in cell and developmental biology · 2023Review
- Review
- Rapamycin improves the quality and developmental competence of mice oocytes by promoting DNA damage repair during in vitro maturation.Reproductive biology and endocrinology : RB&E · 2022Article
- CircRNAs: Roles in regulating head and neck squamous cell carcinoma.Frontiers in oncology · 2022Review
- The Role of Ferroptosis in the Treatment and Drug Resistance of Hepatocellular Carcinoma.Frontiers in cell and developmental biology · 2022Review
- Inhibiting autophagy enhances sulforaphane-induced apoptosisActa pharmaceutica Sinica. B · 2021Article
- The Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging.Oxidative medicine and cellular longevity · 2021Review
- Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2).Neuropsychiatric disease and treatment · 2021Article
- High Levels of Frataxin Overexpression Lead to Mitochondrial and Cardiac Toxicity in Mouse Models.Molecular therapy. Methods & clinical development · 2020Article
- Revisiting cancer hallmarks: insights from the interplay between oxidative stress and non-coding RNAs.Molecular biomedicine · 2020Review
- Crosstalk between noncoding RNAs and ferroptosis: new dawn for overcoming cancer progression.Cell death & disease · 2020Review
- LncRNA NEAT1/miR-129/Bcl-2 signaling axis contributes to HDAC inhibitor tolerance in nasopharyngeal cancer.Aging · 2020Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histone deacetylase inhibitors (HDACis) are the recommended treatment for many solid tumors; however, resistance is a major clinical obstacle for their efficacy. High levels of the transcription factor nuclear factor erythroid 2 like-2 (Nrf2) in cancer cells suggest a vital role in chemoresistance, and regulation of autophagy is one mechanism by which Nrf2 mediates chemoresistance. Although the molecular mechanisms underlying this activity are unclear, understanding them may ultimately improve therapeutic outcomes following HDACi treatment. In this study, we found that HDACi treatment increased Nrf2 mRNA and protein levels and enhanced Nrf2 transcriptional activity. Conversely, Nrf2 knockdown or inhibition blocked HDACi-induced autophagy. In addition, a microRNA (miRNA) array identified upregulation of miR-129-3p in response to Nrf2 overexpression. Chromatin immunoprecipitation assays confirmed miR-129-3p to be a direct Nrf2 target. RepTar and RNAhybrid databases indicated mammalian target of rapamycin (mTOR) as a potential miR-129-3p target, which we experimentally confirmed. Finally, Nrf2 inhibition or miR-129-3p in combination with HDACis increased cell death in vitro and in vivo. Collectively, these results demonstrated that Nrf2 regulates mTOR during HDACi-induced autophagy through miRNA-129-3p and inhibition of this pathway could enhance HDACi-mediated cell death.
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