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通过外泌体递送miR-155抑制剂可经由PTEN和DUSP14抑制三阴性乳腺癌的迁移、侵袭及血管生成。

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

作者信息

Razaviyan Javad, Sirati-Sabet Majid, Hadavi Razie, Karima Saeed, Rajabi Bazl Masoumeh, Mohammadi-Yeganeh Samira

机构信息

Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Curr Med Chem. 2024 Oct 31. doi: 10.2174/0109298673341499241016110341.

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.

摘要

引言

三阴性乳腺癌(TNBC)是最常见的乳腺癌类型。为了开发针对TNBC的有效治疗方法,识别潜在的治疗靶点至关重要。血管生成刺激TNBC中的肿瘤生长和转移,而miR-155在此过程中起关键作用。外泌体是一种纳米大小的囊泡,携带包括miRNA在内的多种物质。本研究调查了外泌体递送miR-155拮抗剂对TNBC中肿瘤迁移、侵袭和血管生成的影响。

材料与方法

从MDA-MB-231细胞中提取外泌体,进行表征,并通过电穿孔加载miR-155拮抗剂。使用RTqPCR分析miR-155及其靶基因(包括PTEN和DUSP14)的表达。采用伤口愈合试验和Transwell试验测量细胞迁移和侵袭。此外,通过管腔形成试验和鸡胚绒毛尿囊膜(CAM)试验评估血管生成。

结果

结果表明,将miR-155拮抗剂通过外泌体递送至人脐静脉内皮细胞(HUVEC)可显著抑制miR-155表达,同时上调PTEN和DUSP14。用含有miR-155拮抗剂的外泌体处理后,HUVEC细胞的管腔形成能力也显著降低,这些结果通过CAM试验得到证实。用加载了miR-155拮抗剂的外泌体处理后,MDA-MB-231细胞的迁移和侵袭显著减少。

结论

发现通过外泌体递送miR-155拮抗剂可通过PTEN和DUSP14抑制TNBC中的迁移、侵袭和血管生成。

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