{"title":"Exosomal miR-3529-3p increases the sensitivity of trastuzumab via Wnt/β-catenin signaling pathway by targeting HOOK3","authors":"Junwen Zhu , Ying Lu , Qingyuan Zhang","doi":"10.1016/j.intimp.2025.115160","DOIUrl":null,"url":null,"abstract":"<div><div>Trastuzumab is frequently utilized to treat human epidermal growth factor receptor 2 (HER2)-positive breast cancer, though its effectiveness is frequently hindered by the development of chemotherapy resistance. Recent research has indicated that exosomes, serving as carriers for genetic material exchanged among diverse tumor cell populations, contribute to the transmission of drug resistance, thereby promoting cancer progression. However, the exact mechanisms through which exosomes originating from breast cancer influence drug resistance remain unclear. In this study, we performed sequencing on exosomes both before and after trastuzumab treatment. Our results demonstrated a significant reduction in miR-3529-3p levels in exosomes from breast cancer patients following trastuzumab treatment compared to pre-treatment levels. Furthermore, miR-3529-3p was also downregulated in cells resistant to trastuzumab. Notably, overexpressing miR-3529-3p counteracted trastuzumab resistance. Additionally, miR-3529-3p mitigated chemoresistance by inhibiting the Wnt signaling pathway through positively regulating HOOK3 expression. In summary, miR-3529-3p in exosomes plays a crucial role in overcoming trastuzumab resistance, highlighting its potential as both a therapeutic target and a prognostic marker for individuals with breast cancer.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"162 ","pages":"Article 115160"},"PeriodicalIF":4.7000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576925011506","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Trastuzumab is frequently utilized to treat human epidermal growth factor receptor 2 (HER2)-positive breast cancer, though its effectiveness is frequently hindered by the development of chemotherapy resistance. Recent research has indicated that exosomes, serving as carriers for genetic material exchanged among diverse tumor cell populations, contribute to the transmission of drug resistance, thereby promoting cancer progression. However, the exact mechanisms through which exosomes originating from breast cancer influence drug resistance remain unclear. In this study, we performed sequencing on exosomes both before and after trastuzumab treatment. Our results demonstrated a significant reduction in miR-3529-3p levels in exosomes from breast cancer patients following trastuzumab treatment compared to pre-treatment levels. Furthermore, miR-3529-3p was also downregulated in cells resistant to trastuzumab. Notably, overexpressing miR-3529-3p counteracted trastuzumab resistance. Additionally, miR-3529-3p mitigated chemoresistance by inhibiting the Wnt signaling pathway through positively regulating HOOK3 expression. In summary, miR-3529-3p in exosomes plays a crucial role in overcoming trastuzumab resistance, highlighting its potential as both a therapeutic target and a prognostic marker for individuals with breast cancer.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.