Exosomal Delivery of miR-155 Inhibitor can Suppress Migration, Invasion, and Angiogenesis Via PTEN and DUSP14 in Triple-negative Breast Cancer.

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Current medicinal chemistry Pub Date : 2024-10-31 DOI:10.2174/0109298673341499241016110341
Javad Razaviyan, Majid Sirati-Sabet, Razie Hadavi, Saeed Karima, Masoumeh Rajabi Bazl, Samira Mohammadi-Yeganeh
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Abstract

Introduction: Triple-Negative Breast Cancer (TNBC) is the most common type of breast cancer (BC). In order to develop effective treatments for TNBC, it is vital to identify potential therapeutic targets. Angiogenesis stimulates tumor growth and metastasis in TNBC, and miR-155 plays a crucial role in this process. The exosome is a nano-sized vesicle that carries many cargoes, including miRNAs. The present study investigated the effect of exosomal delivery of miR-155 antagomir on tumor migration, invasion, and angiogenesis in TNBC.

Materials and methods: From MDA-MB-231 cells, exosomes were extracted, characterized, and loaded with miR-155 antagomir using electroporation. The expression of miR-155 and its target genes, including PTEN and DUSP14, was analyzed using RTqPCR. The wound-healing and transwell assays were used to measure cell migration and invasion. Furthermore, angiogenesis was evaluated by tube formation and chorioallantoic membrane (CAM) assays.

Results: The results indicated that exosomal delivery of miR-155 antagomir to HUVEC cells significantly suppressed miR-155 expression while upregulating PTEN and DUSP14. The tube formation properties of HUVEC cells were also significantly reduced following treatment with exosomes containing miR-155 antagomirs, and these results were confirmed using CAM assay. The migration and invasion of MDA-MB-231 cells were significantly reduced after treatment with miR-155 antagomir-loaded exosomes.

Conclusion: It was found that miR-155 antagomir delivery using exosomes can inhibit migration, invasion, and angiogenesis viaPTEN and DUSP14 in TNBC.

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外泌体输送 miR-155 抑制剂可通过 PTEN 和 DUSP14 抑制三阴性乳腺癌的迁移、侵袭和血管生成
导言三阴性乳腺癌(TNBC)是最常见的乳腺癌(BC)类型。为了开发 TNBC 的有效治疗方法,确定潜在的治疗靶点至关重要。血管生成会刺激 TNBC 中肿瘤的生长和转移,而 miR-155 在这一过程中起着至关重要的作用。外泌体是一种纳米大小的囊泡,可携带多种货物,包括 miRNA。本研究探讨了外泌体递送 miR-155 antagomir 对 TNBC 肿瘤迁移、侵袭和血管生成的影响:从 MDA-MB-231 细胞中提取外泌体,对其进行表征,并使用电穿孔法装载 miR-155 antagomir。使用 RTqPCR 分析了 miR-155 及其靶基因(包括 PTEN 和 DUSP14)的表达。伤口愈合和跨孔试验用于测量细胞迁移和侵袭。此外,还通过管形成和绒毛膜(CAM)试验评估了血管生成:结果表明,向 HUVEC 细胞外泌体递送 miR-155 antagomir 能显著抑制 miR-155 的表达,同时上调 PTEN 和 DUSP14。用含有 miR-155 antagomirs 的外泌体处理 HUVEC 细胞后,其管形成特性也明显降低,这些结果在 CAM 试验中得到了证实。用含有 miR-155 抗配体的外泌体处理后,MDA-MB-231 细胞的迁移和侵袭能力显著降低:结论:研究发现,利用外泌体递送miR-155抗配体可以通过PTEN和DUSP14抑制TNBC细胞的迁移、侵袭和血管生成。
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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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