ArticleCell death & disease2019
MicroRNA-421 confers paclitaxel resistance by binding to the KEAP1 3'UTR and predicts poor survival in non-small cell lung cancer.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 89 citations in OpenAlex.
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- Decoding the NRF2-NOTCH Crosstalk in Lung Cancer-An Update.Antioxidants (Basel, Switzerland) · 2025Review
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- MicroRNAs in lung cancer: their role in tumor progression, biomarkers, diagnostic, prognostic, and therapeutic relevance.Discover oncology · 2025Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders.Cell communication and signaling : CCS · 2024Review
- Article
- MicroRNA 421 induces the formation of high-invasive cell subsets of ovarian cancer from low-invasive cell subsets mediated by exosomes by activating the PI3K/AKT pathway.American journal of cancer research · 2024Article
- Circ_MACF1 targets miR-421 to upregulate FMO2 to suppress paclitaxel resistance and malignant cellular behaviors in lung adenocarcinoma.Thoracic cancer · 2023Article
- Review
- Diagnostic applications and therapeutic option of Cascade CRISPR/Cas in the modulation of miRNA in diverse cancers: promises and obstacles.Journal of cancer research and clinical oncology · 2023Review
- Role of microRNAs in regulation of doxorubicin and paclitaxel responses in lung tumor cells.Cell division · 2023Review
- miR-183-5p regulates ECM and EMT to promote non-small cell lung cancer progression by targeting LOXL4.Journal of thoracic disease · 2023Article
- Applications and advancements of CRISPR-Cas in the treatment of lung cancer.Frontiers in cell and developmental biology · 2023Review
- Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson's Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway.Antioxidants (Basel, Switzerland) · 2022Article
- Epigenetic underpinnings of inflammation: Connecting the dots between pulmonary diseases, lung cancer and COVID-19.Seminars in cancer biology · 2022Review
- MiRNAs in Lung Cancer: Diagnostic, Prognostic, and Therapeutic Potential.Diagnostics (Basel, Switzerland) · 2022Review
- Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer.British journal of cancer · 2022Review
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
MicroRNAs regulate post-transcriptional gene expression and play important roles in multiple cellular processes. In this study, we found that miR-421 suppresses kelch-like ECH-associated protein 1(KEAP1) expression by targeting its 3'-untranslated region (3'UTR). A Q-PCR assay demonstrated that miR-421 is overexpressed in non-small cell lung cancer (NSCLC), especially in A549 cells. Consistently, the level of miR-421 was higher in clinical blood samples from lung cancer patients than in those from normal healthy donors, suggesting that miR-421 is an important lung cancer biomarker. Interestingly, overexpression of miR-421 reduced the level of KEAP1 expression, which further promoted lung cancer cell migration and invasion, as well as inhibited cell apoptosis both in vivo and in vitro. Furthermore, knockdown of miR-421 expression with an antisense morpholino oligonucleotide (AMO) increased ROS levels and treatment sensitivity to paclitaxel in vitro and in vivo, indicating that high miR-421 expression may at least partly account for paclitaxel tolerance in lung cancer patients. To find the upstream regulator of miR-421, one of the candidates, β-catenin, was knocked out via the CRISPR/Cas9 method in A549 cells. Our data showed that inhibiting β-catenin reduced miR-421 levels in A549 cells. In addition, β-catenin upregulation enhanced miR-421 expression, indicating that β-catenin regulates the expression of miR-421 in lung cancer. Taken together, our findings reveal the critical role of miR-421 in paclitaxel drug resistance and its upstream and downstream regulatory mechanisms. Therefore, miR-421 may serve as a potential molecular therapeutic target in lung cancer, and AMOs may be a potential treatment strategy.
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