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探索miR-301a-3p与骨肉瘤:从表达差异到作用机制

Exploring miR-301a-3p and osteosarcoma: from expression differences to mechanism of action.

作者信息

Liu Tianying, Ma Mintao

机构信息

Department of Ultrasonography, Xidian Group Hospital, Xi'An, 710077, China.

Department of Ultrasound, The Affiliated Hospital of Northwest University/Xi'An No.3 Hospital, No. 10, East Section of Fengcheng 3rd Road, Weiyang District, Xi'An, 710021, China.

出版信息

Discov Oncol. 2025 May 13;16(1):751. doi: 10.1007/s12672-025-02345-1.

DOI:10.1007/s12672-025-02345-1
PMID:40358660
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12075034/
Abstract

OBJECTIVES

The pathogenesis of osteosarcoma remains inadequately understood. This study aims to investigate the role and underlying mechanisms of miR-301a-3p in osteosarcoma progression, providing a scientific basis for the development of effective therapeutic strategies.

METHODS

Osteosarcoma tissues and cells were collected and miR-301a-3p expression was detected by qRT-PCR and assessed the correlation between miR-301a-3p expression and clinical disease and prognosis of osteosarcoma patients. The effects of miR-301a-3p overexpression on osteosarcoma cells were investigated by Transwell assay and CCK-8 assay. The targeting relationship between miR-301a-3p and MAFB was detected by dual luciferase reporter assay.

RESULTS

miR-301a-3p was significantly downregulated in osteosarcoma. Significant differences in TNM staging and lung metastasis were observed between the high and low miR-301a-3p expression groups, with a higher mortality rate in the low expression group, indicating it as a risk factor for poor prognosis. Upregulation of miR-301a-3p inhibited the proliferation and metastasis of osteosarcoma cells. MAFB was identified as a target gene of miR-301a-3p, capable of reversing the inhibitory effects of miR-301a-3p on cancer cells.

CONCLUSIONS

Low expression of miR-301a-3p may serve as a warning sign for disease progression and poor prognosis in osteosarcoma patients. miR-301a-3p may inhibit malignant behaviors of osteosarcoma cells by targeting MAFB. Future studies could explore the integration of ultrasound-targeted microbubble destruction technology to enhance the targeted delivery of miR-301a-3p mimics or MAFB inhibitors, potentially overcoming limitations in drug penetration and bioavailability observed in conventional therapies.

摘要

目的

骨肉瘤的发病机制仍未得到充分了解。本研究旨在探讨miR-301a-3p在骨肉瘤进展中的作用及潜在机制,为制定有效的治疗策略提供科学依据。

方法

收集骨肉瘤组织和细胞,采用qRT-PCR检测miR-301a-3p表达,并评估miR-301a-3p表达与骨肉瘤患者临床疾病及预后的相关性。通过Transwell实验和CCK-8实验研究miR-301a-3p过表达对骨肉瘤细胞的影响。采用双荧光素酶报告基因实验检测miR-301a-3p与MAFB之间的靶向关系。

结果

miR-301a-3p在骨肉瘤中显著下调。miR-301a-3p高表达组和低表达组在TNM分期和肺转移方面存在显著差异,低表达组死亡率更高,表明其为预后不良的危险因素。miR-301a-3p的上调抑制了骨肉瘤细胞的增殖和转移。MAFB被鉴定为miR-301a-3p的靶基因,能够逆转miR-301a-3p对癌细胞的抑制作用。

结论

miR-301a-3p低表达可能是骨肉瘤患者疾病进展和预后不良的警示信号。miR-301a-3p可能通过靶向MAFB抑制骨肉瘤细胞的恶性行为。未来的研究可以探索整合超声靶向微泡破坏技术,以增强miR-301a-3p模拟物或MAFB抑制剂的靶向递送,可能克服传统疗法中观察到的药物渗透和生物利用度方面的限制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/89bf83e9fa60/12672_2025_2345_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/6d1cac730e1f/12672_2025_2345_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/3d00801465e6/12672_2025_2345_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/89bf83e9fa60/12672_2025_2345_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/6d1cac730e1f/12672_2025_2345_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/3d00801465e6/12672_2025_2345_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/690c/12075034/89bf83e9fa60/12672_2025_2345_Fig3_HTML.jpg

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