ArticleGastroenterology2018
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
Article in Gastroenterology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 4 of them syntheses that pooled it.
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Who cites it
70 citing papers in PubMed, 4 syntheses or guidelines pooled it, 113 citations in OpenAlex.
- Criteria for preclinical models of cholangiocarcinoma: scientific and medical relevance.Nature reviews. Gastroenterology & hepatology · 2023Guideline
- Molecular Targets and Signaling Pathways in Cholangiocarcinoma: A Systematic Review.Asian Pacific journal of cancer prevention : APJCP · 2023Pooled it
- Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.Nature communications · 2021Pooled it
- Organoids of liver diseases: From bench to bedside.World journal of gastroenterology · 2019Pooled it
- Influence of genomic retained heterosis on lactation persistence and tropical resilience: leveraging joint-model GWAS to quantify non-additive variance in India's Karan Fries population.Tropical animal health and production · 2026Article
- Dissecting Cancer Metabolism and Therapeutic Resistance Using In Vitro Platforms.Advances in experimental medicine and biology · 2026Review
- State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- [Liver organoid technology and its related progress in liver disease research].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Review
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Screening and molecular mechanism research on bile microRNAs associated with chemotherapy efficacy in perihilar cholangiocarcinoma.iScience · 2024Article
- Noncoding RNAs in chronic obstructive pulmonary disease: From pathogenesis to therapeutic targets.Non-coding RNA research · 2024Review
- Human Hepatobiliary Organoids: Recent Advances in Drug Toxicity Verification and Drug Screening.Biomolecules · 2024Review
- Systemic analysis of the prognostic significance and interaction network of miR-26b-3p in cholangiocarcinoma.Applied biochemistry and biotechnology · 2024Article
- A MiR181/Sirtuin1 regulatory circuit modulates drug response in biliary cancers.Clinical and experimental medicine · 2024Article
- Identification and validation of a new prognostic signature based on cancer-associated fibroblast-driven genes in breast cancer.World journal of clinical cases · 2024Article
- Analysis of ddRAD-seq data provides new insights into the genomic structure and patterns of diversity in Italian donkey populations.Journal of animal science · 2024Article
- Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research.Frontiers in cell and developmental biology · 2024Review
- Flourishing tumor organoids: History, emerging technology, and application.Bioengineering & translational medicine · 2023Review
- Review
- A redox-responsive self-assembling COA-4-arm PEG prodrug nanosystem for dual drug delivery suppresses cancer metastasis and drug resistance by downregulating hsp90 expression.Acta pharmaceutica Sinica. B · 2023Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
34 authors at 7 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsCholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.
methodsWe performed a high-throughput screen of 484 small-molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice.
resultsCells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heat shock protein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of patient-derived organoids to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21.
conclusionsmiRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitors might be developed for the treatment of CCA and miRNA21 might be a marker of sensitivity to these agents.
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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.