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微小RNA-125a通过直接靶向骨肉瘤中的E2F2调控细胞增殖。

MicroRNA-125a Regulates Cell Proliferation Via Directly Targeting E2F2 in Osteosarcoma.

作者信息

Tao Tieying, Shen Qinrong, Luo Jianmin, Xu Yang, Liang Wenqing

机构信息

Department of Orthopedics, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, China.

Department of Orthopedics, Shaoxing Hospital of Zhejiang University, Shaoxing, China.

出版信息

Cell Physiol Biochem. 2017;43(2):768-774. doi: 10.1159/000481560. Epub 2017 Sep 27.

Abstract

BACKGROUND/AIMS: Increasing evidence has shown that miR-125a plays important role in human cancer progression. However, little is known about the function of miR-125a in osteosarcoma.

METHODS

The expression of miR-125a in osteosarcoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-125a in osteosarcoma cell proliferation was examined in vitro. The targets of miR-125a were identified by a dual-luciferase reporter assay.

RESULTS

The results showed that the expression of miR-125a expression is significantly lower in osteosarcoma tissues and cell lines. Survival curves showed that the survival of patients in high miR-125a expression was significantly longer than that of patients with low miR-125a expression, and multivariate analysis suggested that miR-125a is an independent prognostic factor for osteosarcoma patients. In addition, it was found in this study that miR-125a can inhibit the growth of osteosarcoma cells. The dual-luciferase reporter assay demonstrated that E2F2 is a novel target gene for miR-125a. In addition, in a recovery experiment, it was shown that miR-125a inhibits the biological function of osteosarcoma cells by inhibiting the expression of E2F2.

CONCLUSION

Our results suggest that miR-125a acts as a tumor suppressor via regulation of E2F2 expression in osteosarcoma progression, and miR-125a may represent a novel therapeutic target for the treatment of osteosarcoma.

摘要

背景/目的:越来越多的证据表明,miR-125a在人类癌症进展中发挥重要作用。然而,关于miR-125a在骨肉瘤中的功能知之甚少。

方法

采用qRT-PCR检测miR-125a在骨肉瘤组织和细胞系中的表达。体外检测miR-125a在骨肉瘤细胞增殖中的生物学作用。通过双荧光素酶报告基因检测鉴定miR-125a的靶标。

结果

结果显示,miR-125a在骨肉瘤组织和细胞系中的表达显著降低。生存曲线显示,miR-125a高表达患者的生存期明显长于miR-125a低表达患者,多因素分析表明miR-125a是骨肉瘤患者的独立预后因素。此外,本研究发现miR-125a可抑制骨肉瘤细胞的生长。双荧光素酶报告基因检测表明E2F2是miR-125a的一个新靶基因。此外,在一项回复实验中,结果显示miR-125a通过抑制E2F2的表达来抑制骨肉瘤细胞的生物学功能。

结论

我们的结果表明,miR-125a在骨肉瘤进展中通过调节E2F2的表达发挥肿瘤抑制作用,miR-125a可能是骨肉瘤治疗的一个新的治疗靶点。

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