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微小RNA-875-5p偶联的金纳米颗粒通过MTDH/PTEN/AKT信号通路抑制乳腺癌进展。

microRNA-875-5p-conjugated gold nanoparticles suppress breast cancer progression through the MTDH/PTEN/AKT signaling pathway.

作者信息

Xiong Bin, Zhang Junfeng, Si Yanmei, Fu Jia

机构信息

School of Clinical Medicine, Jining Medical University, Jining City, 272067, Shandong Province, China.

School of Basic Medicine, Jining Medical University, No. 133 Hehua Road, Taibai Lake District, Jining City, 272067, Shandong Province, China.

出版信息

Discov Oncol. 2024 Dec 18;15(1):804. doi: 10.1007/s12672-024-01626-5.

DOI:10.1007/s12672-024-01626-5
PMID:39692921
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11655799/
Abstract

OBJECTIVE

A lack of effective delivery methods has hampered the study of therapeutics targeting miR-875-5p for breast cancer (BC).

METHODS

The miR-875-5p mimic was conjugated to AuNPs to produce AuNP-miR-875-5p. Then, the effect of AuNP-miR-875-5p on the proliferative, migratory, invasive activities, and apoptosis of BC cells was detected, as well as on tumor growth in animals. The involvement of the MTDH/PTEN/AKT pathway in miR-875-5p-mediated BC progression was identified.

RESULTS

AuNP-miR-875-5p was delivered to BC cells and hampered cell malignancy. MTDH was targeted by miR-875-5p. MTDH expression was negatively correlated with miR-875-5p expression in BC tissues. The anti-tumor effect of AuNP-miR-875-5p in BC cells was counteracted by MTDH overexpression. AuNP-miR-875-5p enhanced PTEN protein expression, thereby inhibiting AKT activation by targeting MTDH. AuNP-miR-875-5p blocked MCF-7 tumor growth in vivo.

CONCLUSION

AuNPs can deliver miR-875-5p to BC cells, and AuNP-miR-875-5p has clinical potential for treating unresectable BC.

摘要

目的

缺乏有效的递送方法阻碍了针对乳腺癌（BC）的miR-875-5p治疗学研究。

方法

将miR-875-5p模拟物与金纳米颗粒（AuNPs）偶联以制备AuNP-miR-875-5p。然后，检测AuNP-miR-875-5p对BC细胞增殖、迁移、侵袭活性和凋亡的影响，以及对动物肿瘤生长的影响。确定MTDH/PTEN/AKT通路在miR-875-5p介导的BC进展中的作用。

结果

AuNP-miR-875-5p被递送至BC细胞并抑制细胞恶性程度。MTDH是miR-875-5p的靶标。在BC组织中，MTDH表达与miR-875-5p表达呈负相关。MTDH过表达抵消了AuNP-miR-875-5p在BC细胞中的抗肿瘤作用。AuNP-miR-875-5p增强PTEN蛋白表达，从而通过靶向MTDH抑制AKT激活。AuNP-miR-875-5p在体内阻断MCF-7肿瘤生长。

结论

AuNPs可将miR-875-5p递送至BC细胞，且AuNP-miR-875-5p在治疗不可切除BC方面具有临床潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/bc9ba0699178/12672_2024_1626_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/c226afc61e21/12672_2024_1626_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/b8ab70d3148d/12672_2024_1626_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/8315124df90e/12672_2024_1626_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/024c9cc97f82/12672_2024_1626_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/ec79894efa66/12672_2024_1626_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/1c22a63aa682/12672_2024_1626_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/bc9ba0699178/12672_2024_1626_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/c226afc61e21/12672_2024_1626_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/b8ab70d3148d/12672_2024_1626_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/8315124df90e/12672_2024_1626_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/024c9cc97f82/12672_2024_1626_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/ec79894efa66/12672_2024_1626_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/1c22a63aa682/12672_2024_1626_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9894/11655799/bc9ba0699178/12672_2024_1626_Fig7_HTML.jpg

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