Exosomal miR-3529-3p increases the sensitivity of trastuzumab via Wnt/β-catenin signaling pathway by targeting HOOK3

IF 4.7 2区 医学 Q2 IMMUNOLOGY
Junwen Zhu , Ying Lu , Qingyuan Zhang
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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.

Abstract Image

外泌体miR-3529-3p通过Wnt/β-catenin信号通路靶向HOOK3增加曲妥珠单抗的敏感性
曲妥珠单抗经常用于治疗人表皮生长因子受体2 (HER2)阳性乳腺癌,尽管其有效性经常因化疗耐药性的发展而受到阻碍。最近的研究表明,外泌体作为不同肿瘤细胞群之间遗传物质交换的载体,有助于耐药性的传播,从而促进癌症的进展。然而,起源于乳腺癌的外泌体影响耐药的确切机制尚不清楚。在这项研究中,我们在曲妥珠单抗治疗前后对外泌体进行了测序。我们的研究结果表明,与治疗前相比,曲妥珠单抗治疗后乳腺癌患者外泌体中miR-3529-3p水平显著降低。此外,miR-3529-3p在曲妥珠单抗耐药细胞中也下调。值得注意的是,过表达miR-3529-3p抵消了曲妥珠单抗耐药。此外,miR-3529-3p通过正向调节HOOK3表达抑制Wnt信号通路,从而减轻化学耐药。总之,外泌体中的miR-3529-3p在克服曲珠单抗耐药中起着至关重要的作用,突出了其作为乳腺癌个体的治疗靶点和预后标志物的潜力。
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来源期刊
CiteScore
8.40
自引率
3.60%
发文量
935
审稿时长
53 days
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.
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