ArticleInternational journal of cancer2012
Let-7 modulates acquired resistance of ovarian cancer to Taxanes via IMP-1-mediated stabilization of multidrug resistance 1.
Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 163 citations in OpenAlex.
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- The biological roles and molecular mechanisms of m6A reader IGF2BP1 in the hallmarks of cancer.Genes & diseases · 2025Review
- MiRNAs: main players of cancer drug resistance target ABC transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Interleukin-6 Modulation in Ovarian Cancer Necessitates a Targeted Strategy: From the Approved to Emerging Therapies.Cancers · 2024Review
- Epigenetic Activation of the CMTM6-IGF2BP1-EP300 Positive Feedback Loop Drives Gemcitabine Resistance in Pancreatic Ductal Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Exosomal microRNA as a key regulator of PI3K/AKT pathways in human tumors.Medical oncology (Northwood, London, England) · 2024Review
- Key genes and molecular mechanisms related to Paclitaxel Resistance.Cancer cell international · 2024Review
- The microRNA Let-7 and its exosomal form: Epigenetic regulators of gynecological cancers.Cell biology and toxicology · 2024Review
- IGF2BPs as novel mGenes & diseases · 2024Review
- Regulation of P-Glycoprotein during Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Review
- Current strategies for early epithelial ovarian cancer detection using miRNA as a potential tool.Frontiers in molecular biosciences · 2024Review
- Insulin-like Growth Factor II mRNA-Binding Protein 1 Regulates Pancreatic Cancer Cell Growth through the Surveillance ofCancers · 2023Article
- Elevated expression of the RNA-binding protein IGF2BP1 enhances the mRNA stability of INHBA to promote the invasion and migration of esophageal squamous cancer cells.Experimental hematology & oncology · 2023Article
- Review
- A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer.Molecular cancer · 2023Article
- Metabolic pathways of potential miRNA biomarkers derived from liquid biopsy in epithelial ovarian cancer.Oncology letters · 2023Article
- Evaluation of Serum microRNA Let-7c and Let-7d as Predictive Biomarkers for Metastatic Pancreatic Cancer.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022Article
- Tumor-targeted miRNA nanomedicine for overcoming challenges in immunity and therapeutic resistance.Nanomedicine (London, England) · 2022Review
- Combination microRNA-based cellular reprogramming with paclitaxel enhances therapeutic efficacy in a relapsed and multidrug-resistant model of epithelial ovarian cancer.Molecular therapy oncolytics · 2022Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Ovarian cancer patients frequently develop resistance to chemotherapy regiments using Taxol and carboplatin. One of the resistance factors that protects cancer cells from Taxol-based therapy is multidrug resistance 1 (MDR1). micro(mi)RNAs are small noncoding RNAs that negatively regulate protein expression. Members of the let-7 family of miRNAs are downregulated in many human cancers, and low let-7 expression has been correlated with resistance to microtubule targeting drugs (Taxanes), although little is known that would explain this activity. We now provide evidence that, although let-7 is not a universal sensitizer of cancer cells to Taxanes, it affects acquired resistance of cells to this class of drugs by targeting IMP-1, resulting in destabilization of the mRNA of MDR1. Introducing let-7g into ADR-RES cells expressing both IMP-1 and MDR1 reduced expression of both proteins rendering the cells more sensitive to treatment with either Taxol or vinblastine without affecting the sensitivity of the cells to carboplatin, a non-MDR1 substrate. This effect could be reversed by reintroducing IMP-1 into let-7g high/MDR1 low cells causing MDR1 to again become stabilized. Consistently, many relapsed ovarian cancer patients tested before and after chemotherapy were found to downregulate let-7 and to co-upregulate IMP-1 and MDR1, and the increase in the expression levels of both proteins after chemotherapy negatively correlated with disease-free time before recurrence. Our data point at IMP-1 and MDR1 as indicators for response to therapy, and at IMP-1 as a novel therapeutic target for overcoming multidrug resistance of ovarian cancer.
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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.