ArticleBMC cancer2021
EHHADH contributes to cisplatin resistance through regulation by tumor-suppressive microRNAs in bladder cancer.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 62 citations in OpenAlex.
- Therapeutic strategies for MMAE-resistant bladder cancer through DPP4 inhibition.Molecular oncology · 2026Article
- Comprehensive pan-cancer analysis and experimental verification of the roles of SCP2 in colon adenocarcinoma.BMC cancer · 2026Article
- Review
- A prognostic model for basal-like breast cancer based on beta-alanine metabolism genes: EHHADH as a potential biomarker and target for drug screening.Genes & genomics · 2025Article
- Clinical relevance of Nectin-4 downregulation and biological changes caused by cytotoxic chemotherapy in bladder cancer.Cancer chemotherapy and pharmacology · 2025Article
- Lipidomics reveals effect of EHHADH in lung squamous cell.Cell biology and toxicology · 2025Article
- LncRNA Gm35585 transcriptionally activates the peroxidase EHHADH against diet-induced fatty liver.Experimental & molecular medicine · 2025Article
- Development of a novel treatment based on PKMYT1 inhibition for cisplatin-resistant bladder cancer with miR-424-5p-dependent cyclin E1 amplification.BMC cancer · 2024Article
- Targeting metabolic reprogramming to overcome drug resistance in advanced bladder cancer: insights from gemcitabine- and cisplatin-resistant models.Molecular oncology · 2024Article
- LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer.International journal of molecular sciences · 2024Article
- A novel lipid metabolism-based risk model associated with immunosuppressive mechanisms in diffuse large B-cell lymphoma.Lipids in health and disease · 2024Article
- Serum EZH2 is a novel biomarker for bladder cancer diagnosis and prognosis.Frontiers in oncology · 2024Article
- Identification of differentially expressed miRNAs and mRNAs associated with the regulation of breast cancer via in silico and in vitro methods.Cytotechnology · 2023Article
- Identification of Somatic Mutations in Plasma Cell-Free DNA from Patients with Metastatic Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2023Article
- Characterization and treatment of gemcitabine- and cisplatin-resistant bladder cancer cells with a pan-RAS inhibitor.FEBS open bio · 2023Article
- [EHHADH is a key gene in fatty acid metabolism pathways in hepatocellular carcinoma: a transcriptomic analysis].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment.International journal of molecular sciences · 2023Review
- Review
- Article
- microRNA-99a-5p induces cellular senescence in gemcitabine-resistant bladder cancer by targeting SMARCD1.Molecular oncology · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCisplatin-based chemotherapy is recommended as the primary treatment for advanced bladder cancer (BC) with unresectable or metastatic disease. However, the benefits are limited due to the acquisition of drug resistance. The mechanisms of resistance remain unclear. Although there are some reports that some molecules are associated with cisplatin resistance in advanced BC, those reports have not been fully investigated. Therefore, we undertook a new search for cisplatin resistance-related genes targeted by tumor suppressive microRNAs as well as genes that were downregulated in cisplatin-resistant BC cells and clinical BC tissues.
methodsFirst, we established cisplatin-resistant BOY and T24 BC cell lines (CDDP-R-BOY, CDDP-R-T24). Then, Next Generation Sequence analysis was performed with parental and cisplatin-resistant cell lines to search for the microRNAs responsible for cisplatin resistance. We conducted gain-of-function analysis of microRNAs and their effects on cisplatin resistance, and we searched target genes comprehensively using Next Generation mRNA sequences.
resultsA total of 28 microRNAs were significantly downregulated in both CDDP-R-BOY and CDDP-R-T24. Among them, miR-486-5p, a tumor suppressor miRNA, was negatively correlated with the TNM classification of clinical BC samples in The Cancer Genome Atlas (TCGA) database. Transfection of miRNA-486-5p significantly inhibited cancer cell proliferation, migration, and invasion, and also improved the cells' resistance to cisplatin. Among the genes targeted by miRNA-486-5p, we focused on enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase (EHHADH), which is involved in the degradation of fatty acids. EHHADH was directly regulated by miRNA-486-5p as determined by a dual-luciferase reporter assay. Loss-of-function study using EHHADH si-RNA showed significant inhibitions of cell proliferation, migration, invasion and the recovery of cisplatin sensitivity.
conclusionIdentification of EHHADH as a target of miRNA-486-5p provides novel insights into the potential mechanisms of cisplatin resistance in BC.
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