ArticleCells2021
miR-140-5p Attenuates Hypoxia-Induced Breast Cancer Progression by Targeting Nrf2/HO-1 Axis in a Keap1-Independent Mechanism.
Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- The role of NRF2 in human cancers: Pre-clinical insights paving the way for clinical trials.Journal of pharmaceutical analysis · 2026Review
- The emerging role of Nrf2 in heart failure: From cardioprotection to therapeutic approaches.ESC heart failure · 2025Review
- Regulatory Roles of miR-155-5p, miR-21-5p, miR-93-5p, and miR-140-5p in Breast Cancer Progression.Current issues in molecular biology · 2025Article
- MiR-556-3p mediated repression of klotho under oxidative stress promotes fibrosis of renal tubular epithelial cells.Scientific reports · 2025Article
- miR-145-5p Inhibits HER2-Positive Breast Cancer Cells via Targeting ARF6.International journal of general medicine · 2025Article
- The signature of extracellular vesicles in hypoxic breast cancer and their therapeutic engineering.Cell communication and signaling : CCS · 2024Review
- The interplay between microRNAs and Nrf2 signaling in human cancers.Cancer cell international · 2024Review
- Sleep and Oxidative Stress: Current Perspectives on the Role of NRF2.Cellular and molecular neurobiology · 2024Review
- Novel Acetamide-Based HO-1 Inhibitor Counteracts Glioblastoma Progression by Interfering with the Hypoxic-Angiogenic Pathway.International journal of molecular sciences · 2024Article
- Nrf2 in human cancers: biological significance and therapeutic potential.American journal of cancer research · 2024Review
- Dexmedetomidine Alleviates Brain Ischemia/Reperfusion Injury by Regulating Metastasis-associated Lung Adenocarcinoma Transcript 1/MicroRNA-140-5p/ Nuclear Factor Erythroid-derived 2-like 2 Axis.Protein and peptide letters · 2024Article
- Role of MicroRNA in Hypoxic Tumours and their Potential as Biomarkers for Early Detection of Cancer.Current molecular medicine · 2024Review
- Antioxidant genes in cancer and metabolic diseases: Focusing on Nrf2, Sestrin, and heme oxygenase 1.International journal of biological sciences · 2024Review
- Regulation of Cancer-Associated miRNAs Expression under Hypoxic Conditions.Analytical cellular pathology (Amsterdam) · 2024Review
- Apigenin inhibits angiogenesis in retinal microvascular endothelial cells through regulating of the miR-140-5p/HDAC3-mediated PTEN/PI3K/AKT pathway.BMC ophthalmology · 2023Article
- MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate.International journal of molecular sciences · 2023Review
- Hypoxia-driven ncRNAs in breast cancer.Frontiers in oncology · 2023Review
- Review
- Picrasidine I Triggers Heme Oxygenase-1-Induced Apoptosis in Nasopharyngeal Carcinoma Cells via ERK and Akt Signaling Pathways.International journal of molecular sciences · 2022Article
- New insights into the interplay between autophagy and oxidative and endoplasmic reticulum stress in neuronal cell death and survival.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia and oxidative stress significantly contribute to breast cancer (BC) progression. Although hypoxia-inducible factor 1α (Hif-1α) is considered a key effector of the cellular response to hypoxia, nuclear factor erythroid 2-related factor 2 (Nrf2), a master antioxidant transcription factor, is a crucial factor essential for Hif-1α-mediated hypoxic responses. Hence, targeting Nrf2 could provide new treatment strategies for cancer therapy. miRNAs are potential regulators of hypoxia-responsive genes. In a quest to identify novel hypoxia-regulated miRNAs involved in the regulation of Nrf2, we found that miR-140-5p significantly affects the expression of Nrf2 under hypoxia. In our study, miR-140-5p expression is downregulated in BC cells under hypoxic conditions. We have identified Nrf2 as a direct target of miR-140-5p, as confirmed by the luciferase assay. Knockdown of miR-140-5p under normoxic conditions significantly enhanced Nrf2/HO-1 signaling and tumor growth, angiogenesis, migration, and invasion in BC. In contrast, overexpression of miR-140-5p under hypoxic conditions revealed opposite results. Further silencing Nrf2 expression mimicked the miR-140-5p-induced anti-tumor effects. Consistent with the knockdown of miR-140-5p in vitro, mice injected with miR-140-5p-KD cells exhibited dramatically reduced miR-140-5p levels, increased Nrf2 levels, and increased tumor growth. In contrast, tumor growth is potently suppressed in mice injected with miR-140-5p-OE cells. Collectively, the above results demonstrate the importance of the Nrf2/HO-1 axis in cancer progression and, thus, targeting Nrf2 by miR-140-5p could be a better strategy for the treatment of Nrf2-driven breast cancer progression.
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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.