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微小RNA-449a在骨肉瘤中表达下调,并通过靶向BCL2促进细胞凋亡。

miRNA-449a is downregulated in osteosarcoma and promotes cell apoptosis by targeting BCL2.

作者信息

Chen Jie, Zhou Jinsong, Chen Xin, Yang Baohui, Wang Dong, Yang Pinglin, He Xijing, Li Haopeng

机构信息

Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi'an Jiaotong University, No. 157 Xiwu Road, Xi'an, Shaanxi, 710004, People's Republic of China.

Department of Orthopaedic Surgery, Xi'an No. 5 Hospital, Xi'an, Shaanxi, 710004, People's Republic of China.

出版信息

Tumour Biol. 2015 Sep;36(10):8221-9. doi: 10.1007/s13277-015-3568-y. Epub 2015 May 23.

Abstract

Accumulating evidence reveals that miR-449a is expressed at a low level in several tumors and cancer cell lines, and acts as a tumor suppressor in several cancers. However, its role in osteosarcoma (OS) is not well understood. In the present study, we found that miR-449a was significantly downregulated in both OS tissues and cell lines. Furthermore, low expression level of miR-449a was correlated with advanced tumor stage, metastasis, and predicted a poor overall survival in OS patients. Additionally, restoration of miR-449a in OS cell lines U2OS and Saos-2 reduced cell viability, promoted cell apoptosis in vitro, and suppressed tumorigenicity in vivo. Moreover, BCL2, an antiapoptotic molecule, was identified to be a direct target of miR-449a, and the proapoptotic function of miR-449a was mainly through targeting BCL2 expression. Taken together, our results demonstrated a tumor-suppressive role of miR-449a in OS progression and suggested a potential therapeutic target for OS.

摘要

越来越多的证据表明,miR-449a在多种肿瘤和癌细胞系中表达水平较低,并在多种癌症中发挥肿瘤抑制作用。然而,其在骨肉瘤(OS)中的作用尚不清楚。在本研究中,我们发现miR-449a在OS组织和细胞系中均显著下调。此外,miR-449a的低表达水平与肿瘤晚期、转移相关,并预示OS患者的总体生存率较差。此外,在OS细胞系U2OS和Saos-2中恢复miR-449a可降低细胞活力,促进体外细胞凋亡,并抑制体内致瘤性。此外,抗凋亡分子BCL2被确定为miR-449a的直接靶点,miR-449a的促凋亡功能主要通过靶向BCL2表达实现。综上所述,我们的结果证明了miR-449a在OS进展中的肿瘤抑制作用,并提示其可能成为OS的潜在治疗靶点。

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