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微小RNA-4295通过靶向干扰素调节因子1促进骨肉瘤细胞的增殖、迁移和侵袭。

miR-4295 promotes cell proliferation, migration and invasion of osteosarcoma through targeting interferon regulatory factor 1.

作者信息

Cheng Jin Pei, Huang Bin, Duan Jun Hu, Yi Kai Jun, Zhuang Zheng Ling

机构信息

Department of Orthopaedics, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, Hubei 441000, P.R. China.

出版信息

Oncol Lett. 2020 Nov;20(5):260. doi: 10.3892/ol.2020.12123. Epub 2020 Sep 18.

DOI:10.3892/ol.2020.12123
PMID:32989394
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7517570/
Abstract

Osteosarcoma (OS) is the most common form of primary malignant bone tumor. Despite encouraging progress in the treatment of OS, the survival rate for patients with OS has remained unchanged over the past 40 years. It has been established that miRNA plays a crucial regulatory role in the progression and development of OS. To explore the potential association of miRNAs with OS, bioinformatics techniques were used to screen for differentially expressed miRNA genes in OS in the Gene Expression Omnibus database. In the GSE70367 database, it was revealed that miR-4295 expression was abnormally elevated in the expression of OS cells. To characterize the potential function of miR-4295 in OS, the expression levels of miR-4295 in 30 samples of OS and adjacent normal tissues was examined. The results revealed that the expression of miR-4295 was significantly increased in OS tissues compared with the paired normal tissues. Moreover, the expression levels of miR-4295 in OS cell lines (MG-63 and Saos-2) were significantly higher compared with those in the normal human mesenchymal stem cells. In addition, miR-4295 was associated with OS cell proliferation, migration and invasion. Furthermore, it was demonstrated that the expression of interferon regulatory factor (IRF)1, a tumor suppressor, was regulated by miR-4295 directly in OS cells. Taken together, the present results revealed that miR-4295 may act as a tumor activator by targeting IRF1 during the progression of OS. Investigating miR-4295 may provide novel insight into the mechanisms of OS metastasis, and inhibition and targeting miR-4295 may be a novel therapeutic strategy for the treatment of OS.

摘要

骨肉瘤(OS)是原发性恶性骨肿瘤最常见的形式。尽管在骨肉瘤治疗方面取得了令人鼓舞的进展,但在过去40年里,骨肉瘤患者的生存率一直没有变化。已经确定,miRNA在骨肉瘤的进展和发展中起着关键的调节作用。为了探索miRNA与骨肉瘤的潜在关联,利用生物信息学技术在基因表达综合数据库中筛选骨肉瘤中差异表达的miRNA基因。在GSE70367数据库中,发现miR-4295在骨肉瘤细胞的表达中异常升高。为了表征miR-4295在骨肉瘤中的潜在功能,检测了30例骨肉瘤样本和相邻正常组织中miR-4295的表达水平。结果显示,与配对的正常组织相比,骨肉瘤组织中miR-4295的表达显著增加。此外,与正常人骨髓间充质干细胞相比,骨肉瘤细胞系(MG-63和Saos-2)中miR-4295的表达水平显著更高。此外,miR-4295与骨肉瘤细胞的增殖、迁移和侵袭有关。此外,还证明了肿瘤抑制因子干扰素调节因子(IRF)1的表达在骨肉瘤细胞中直接受miR-4295调控。综上所述,目前的结果表明,在骨肉瘤进展过程中,miR-4295可能通过靶向IRF1发挥肿瘤激活剂的作用。研究miR-4295可能为骨肉瘤转移机制提供新的见解,抑制并靶向miR-4295可能是治疗骨肉瘤的一种新的治疗策略。

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