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微小RNA-490-5p通过靶向组蛋白去乙酰化酶2抑制骨肉瘤进展。

miR-490-5p inhibits the progression of osteosarcoma by targeting HDAC2.

作者信息

Jiang Huiqun, Xia Jiahao, Tao Yuan, Zhang Yu

机构信息

Department of GCP, The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.

Department of Orthopedics, The Second People's Hospital of Changzhou, the Third Affiliated Hospital of Nanjing Medical University, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.

出版信息

Transl Cancer Res. 2025 Jul 30;14(7):4357-4368. doi: 10.21037/tcr-2024-2217. Epub 2025 Jul 22.

Abstract

BACKGROUND

Osteosarcoma (OS) is the most prevalent malignant bone tumor and has a particularly unfavorable prognosis. Although miR-490-5p is regarded as an established diagnostic and predictive marker for human cancers, the role of miR-490-5p in OS remains presently unclear. The aim of this study was to clarify the function of miR-490-5p in OS.

METHODS

Bioinformatics analysis of OS cells was performed to identify differentially expressed microRNAs (miRNAs, miRs). Then, the expression profiles of miR-490-5p in various OS cells were determined by real-time polymerase chain reaction analysis. The roles of miR-490-5p in OS cells were assessed through cytological experiments. Bioinformatics methods were used to predict target genes. The relationship between miR-490-5p and HDAC2 was demonstrated by a dual-luciferase reporter gene assay.

RESULTS

Expression of miR-490-5p was relatively decreased in OS cells. Overexpression of miR-490-5p inhibited proliferation and metastasis of OS cells. Moreover, miR-490-5p was found to negatively regulate HDAC2 as a downstream target gene. Recovery experiments confirmed that HDAC2 overexpression rescued the inhibitory effect on OS progression by overexpression of miR-490-5p.

CONCLUSIONS

MiR-490-5p directly regulated HDAC2 expression, thereby modulating the growth and metastatic capacity of OS cells. The miR-490-5p/HDAC2 axis could serve as a promising therapeutic target for OS.

摘要

背景

骨肉瘤(OS)是最常见的恶性骨肿瘤,预后特别差。尽管miR - 490 - 5p被认为是人类癌症的既定诊断和预测标志物,但miR - 490 - 5p在骨肉瘤中的作用目前仍不清楚。本研究的目的是阐明miR - 490 - 5p在骨肉瘤中的功能。

方法

对骨肉瘤细胞进行生物信息学分析,以鉴定差异表达的 microRNA(miRNA,miR)。然后,通过实时聚合酶链反应分析确定miR - 490 - 5p在各种骨肉瘤细胞中的表达谱。通过细胞学实验评估miR - 490 - 5p在骨肉瘤细胞中的作用。使用生物信息学方法预测靶基因。通过双荧光素酶报告基因测定法证明miR - 490 - 5p与HDAC2之间的关系。

结果

miR - 490 - 5p在骨肉瘤细胞中的表达相对降低。miR - 490 - 5p的过表达抑制了骨肉瘤细胞的增殖和转移。此外,发现miR - 490 - 5p作为下游靶基因对HDAC2具有负调控作用。恢复实验证实,HDAC2的过表达挽救了miR - 490 - 5p过表达对骨肉瘤进展的抑制作用。

结论

miR - 490 - 5p直接调节HDAC2的表达,从而调节骨肉瘤细胞的生长和转移能力。miR - 490 - 5p/HDAC2轴可能成为骨肉瘤有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/061a/12335688/a74b26f81752/tcr-14-07-4357-f1.jpg

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