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微小RNA-330-3p的表达预示骨肉瘤预后良好,并通过靶向Bmi-1抑制细胞增殖。

MicroRNA-330-3p Expression Indicates Good Prognosis and Suppresses Cell Proliferation by Targeting Bmi-1 in Osteosarcoma.

作者信息

Zheng Zhenxin, Bao Feng, Chen Xuhong, Huang Hongbin, Zhang Xiangfeng

机构信息

Department of Orthopedics, Yiwu Central Hospital, Yiwu, China.

Department of Orthopedics, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Cell Physiol Biochem. 2018;46(2):442-450. doi: 10.1159/000488612. Epub 2018 Mar 26.

Abstract

BACKGROUND/AIMS: Growing evidence has shown that miR-330-3p is closely related to the biological behavior of cancer, including proliferation, metastasis, and prognosis. However, there have been no reports on miR-330-3p expression and function in osteosarcoma.

METHODS

Expression of miR-330-3p in osteosarcoma tissues and cell lines was examined by quantitative PCR. Effects of miR-330-3p on osteosarcoma cell proliferation were investigated in vitro with the Cell Counting Kit-8 colorimetric assay. Targets of miR-330-3p were identified by dual-luciferase reporter assay.

RESULTS

The results showed that expression of miR-330 decreased in osteosarcoma tissues and cell lines. Prognosis of patients with high miR-330-3p expression was much better than that of those with low expression (P=0.001), and multivariate analysis suggested that miR-330-3p is an independent prognostic factor for osteosarcoma. In addition, miR-330-3p overexpression significantly inhibited the growth of MG-63 and U2OS osteosarcoma cells. Dual-luciferase reporter assay demonstrated that Bmi-1 was a direct target gene of miR-330-3p, and in a recovery experiment, miR-330-3p suppressed osteosarcoma cell proliferation by directly targeting Bmi-1.

CONCLUSION

Our results suggest that miR-330-3p acts as a tumor suppressor by regulating Bmi-1 expression in osteosarcoma. Thus, miR-330-3p 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-330-3p与癌症的生物学行为密切相关,包括增殖、转移和预后。然而,关于miR-330-3p在骨肉瘤中的表达及功能尚无报道。

方法

采用定量PCR检测骨肉瘤组织和细胞系中miR-330-3p的表达。运用细胞计数试剂盒-8比色法在体外研究miR-330-3p对骨肉瘤细胞增殖的影响。通过双荧光素酶报告基因检测法鉴定miR-330-3p的靶标。

结果

结果显示,骨肉瘤组织和细胞系中miR-330的表达降低。miR-330-3p高表达患者的预后明显优于低表达患者(P=0.001),多因素分析表明miR-330-3p是骨肉瘤的独立预后因素。此外,miR-330-3p过表达显著抑制MG-63和U2OS骨肉瘤细胞的生长。双荧光素酶报告基因检测表明Bmi-1是miR-330-3p的直接靶基因,在回复实验中,miR-330-3p通过直接靶向Bmi-1抑制骨肉瘤细胞增殖。

结论

我们的结果表明,miR-330-3p在骨肉瘤中通过调节Bmi-1的表达发挥肿瘤抑制作用。因此,miR-330-3p可能是治疗骨肉瘤的一个新的治疗靶点。

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