ArticleCancer research2015
Genetic mutation of p53 and suppression of the miR-17∼92 cluster are synthetic lethal in non-small cell lung cancer due to upregulation of vitamin D Signaling.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Association of CYP24A1 with survival and drug resistance in clinical cancer patients: a meta-analysis.BMC cancer · 2022Pooled it
- Article
- Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer.Nutrition & metabolism · 2024Article
- Non-coding RNAs and exosomal non-coding RNAs in lung cancer: insights into their functions.Frontiers in cell and developmental biology · 2024Review
- Review
- Vitamin D Deficiency Impacts Exposure and Response of Pravastatin in Male Rats by Altering Hepatic OATPs.Frontiers in pharmacology · 2022Article
- Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?International journal of molecular sciences · 2021Review
- Frontiers of MicroRNA Signature in Non-small Cell Lung Cancer.Frontiers in cell and developmental biology · 2021Review
- Thiol-Redox Regulation in Lung Development and Vascular Remodeling.Antioxidants & redox signaling · 2019Review
- MicroRNA Networks Modulate Oxidative Stress in Cancer.International journal of molecular sciences · 2019Review
- iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data.BMC bioinformatics · 2018Article
- MiR-192, miR-200c and miR-17 are fibroblast-mediated inhibitors of colorectal cancer invasion.Oncotarget · 2018Article
- The Anti-Inflammatory Effects of Vitamin D in Tumorigenesis.International journal of molecular sciences · 2018Review
- Exploring vitamin D metabolism and function in cancer.Experimental & molecular medicine · 2018Review
- Biology of MiR-17-92 Cluster and Its Progress in Lung Cancer.International journal of medical sciences · 2018Review
- MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non-small cell lung cancer.Cell proliferation · 2017Review
- MicroRNA-30a attenuates mutant KRAS-driven colorectal tumorigenesis via direct suppression of ME1.Cell death and differentiation · 2017Article
- An Excess of CYP24A1, Lack of CaSR, and a Novel lncRNA Near the PTH Gene Characterize an Ectopic PTH-Producing Tumor.Journal of the Endocrine Society · 2017Article
- New insights into vitamin D anticancer properties: focus on miRNA modulation.Molecular genetics and genomics : MGG · 2017Review
- Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention.Non-coding RNA research · 2016Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Lung cancer is the leading cause of cancer-related fatalities. Recent success developing genotypically targeted therapies, with potency only in well-defined subpopulations of tumors, suggests a path to improving patient survival. We used a library of oligonucleotide inhibitors of microRNAs, a class of posttranscriptional gene regulators, to identify novel synthetic lethal interactions between miRNA inhibition and molecular mechanisms in non-small cell lung cancer (NSCLC). Two inhibitors, those for miR-92a and miR-1226*, produced a toxicity distribution across a panel of 27 cell lines that correlated with loss of p53 protein expression. Notably, depletion of p53 was sufficient to confer sensitivity to otherwise resistant telomerase-immortalized bronchial epithelial cells. We found that both miR inhibitors cause sequence-specific downregulation of the miR-17∼92 polycistron, and this downregulation was toxic only in the context of p53 loss. Mechanistic studies indicated that the selective toxicity of miR-17∼92 polycistron inactivation was the consequence of derepression of vitamin D signaling via suppression of CYP24A1, a rate-limiting enzyme in the 1α,25-dihydroxyvitamin D3 metabolic pathway. Of note, high CYP24A1 expression significantly correlated with poor patient outcome in multiple lung cancer cohorts. Our results indicate that the screening approach used in this study can identify clinically relevant synthetic lethal interactions and that vitamin D receptor agonists may show enhanced efficacy in p53-negative lung cancer patients.
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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.