ArticleMolecular cancer2020
CAF secreted miR-522 suppresses ferroptosis and promotes acquired chemo-resistance in gastric cancer.
Article in Molecular cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 671 papers, 7 of them syntheses that pooled it.
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Who cites it
671 citing papers in PubMed, 7 syntheses or guidelines pooled it, 992 citations in OpenAlex.
- Exosomal Non-Coding RNAs in Gastrointestinal Cancer Drug Resistance: A Systematic Review of Emerging Mechanisms and Clinical Implications.Journal of cellular and molecular medicine · 2026Pooled it
- Interaction of HIF-1a with various cell death pathways in tumor immune microenvironment (TIME).Apoptosis : an international journal on programmed cell death · 2026Pooled it
- The mechanism of breast cancer stem cells and tumor microenvironment promoting radioresistance in breast cancer and its intervention strategies.Frontiers in immunology · 2026Pooled it
- Mechanism and role of ferroptosis in the development of gastric cancer.Clinical and experimental medicine · 2025Pooled it
- Pharmacological mechanisms of traditional Chinese medicine in treating gastric cancer: a focus on the ferroptosis regulation.Frontiers in pharmacology · 2025Pooled it
- A comprehensive bibliometric analysis of ferroptosis in tumor resistance: development and emerging trends.Frontiers in immunology · 2025Pooled it
- Global research landscape of ferroptosis in gastric cancer: a multidisciplinary bibliometric analysis based on multiple databases (2017-2025).Frontiers in immunology · 2025Pooled it
- Three-Year Follow-Up of Neoadjuvant Tislelizumab with Chemotherapy in Locally Advanced Gastric and Gastroesophageal Junction Adenocarcinoma: Revealing Cancer-Associated Fibroblast Heterogeneity Corresponding to PD-1 Blockade Efficacy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Trial
- Reprogramming of cell death in gastric cancer: From molecular mechanisms to therapeutic potential (Review).International journal of molecular medicine · 2026Review
- Ferroptosis and tumor microenvironment: orchestrating therapy resistance, immune evasion, and metastatic events.Medical oncology (Northwood, London, England) · 2026Review
- Extracellular Vesicles: Classification, Biological Functions, Diseases, and Therapeutic Opportunities.MedComm · 2026Review
- Inhibition or induction of gastrointestinal tumors by ferroptosis and intervention by herbal extracts (Review).Oncology letters · 2026Review
- Molecular classification and precision therapy in gastric cancer: Current advances and future perspectives (Review).Oncology reports · 2026Review
- Ferroptosis in cancer: molecular mechanisms, biological roles, and therapeutic significance.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Mechanisms of chemoresistance in gastric cancer: interplay between microRNAs and the tumor microenvironment.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Cuproptosis and ferroptosis: signal pathways, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- The Emerging Role of Ferroptosis in Pediatric Cancer Biology and Therapy.International journal of molecular sciences · 2026Review
- Modulation of the tumor microenvironment through BMAL1-LHX8 axis augments the sensitivity of ameloblastoma to vemurafenib.Journal of advanced research · 2026Article
- Integrated OAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer-Associated Fibroblasts Promote Glucose Metabolic Reprogramming and Progression of Triple-Negative Breast Cancer via Exosomal circFAD104-Mediated Intercellular Communication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
611 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFerroptosis is a novel mode of non-apoptotic cell death induced by build-up of toxic lipid peroxides (lipid-ROS) in an iron dependent manner. Cancer-associated fibroblasts (CAFs) support tumor progression and drug resistance by secreting various bioactive substances, including exosomes. Yet, the role of CAFs in regulating lipid metabolism as well as ferroptosis of cancer cells is still unexplored and remains enigmatic.
methodsFerroptosis-related genes in gastric cancer (GC) were screened by using mass spectrum; exosomes were isolated by ultra-centrifugation and CAF secreted miRNAs were determined by RT-qPCR. Erastin was used to induce ferroptosis, and ferroptosis levels were evaluated by measuring lipid-ROS, cell viability and mitochondrial membrane potential.
resultsHere, we provide clinical evidence to show that arachidonate lipoxygenase 15 (ALOX15) is closely related with lipid-ROS production in gastric cancer, and that exosome-miR-522 serves as a potential inhibitor of ALOX15. By using primary stromal cells and cancer cells, we prove that exosome-miR-522 is mainly derived from CAFs in tumor microenvironment. Moreover, heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) was found to mediate miR-522 packing into exosomes, and ubiquitin-specific protease 7 (USP7) stabilizes hnRNPA1 through de-ubiquitination. Importantly, cisplatin and paclitaxel promote miR-522 secretion from CAFs by activating USP7/hnRNPA1 axis, leading to ALOX15 suppression and decreased lipid-ROS accumulation in cancer cells, and ultimately result in decreased chemo-sensitivity.
conclusionsThe present study demonstrates that CAFs secrete exosomal miR-522 to inhibit ferroptosis in cancer cells by targeting ALOX15 and blocking lipid-ROS accumulation. The intercellular pathway, comprising USP7, hnRNPA1, exo-miR-522 and ALOX15, reveals new mechanism of acquired chemo-resistance in GC.
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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.