Wang Fei, Yu Dapeng, Liu Zhen, Wang Ruijie, Xu Yan, Cui Haiyin, Zhao Tingbao
Department of Trauma and Orthopedics, Institute of Chinese People's Liberation Army, General Hospital of Jinan Military Command, Jinan, China
Department of Trauma and Orthopedics, Institute of Chinese People's Liberation Army, General Hospital of Jinan Military Command, Jinan, China.
Technol Cancer Res Treat. 2016 Dec;15(6):NP105-NP112. doi: 10.1177/1533034615618849. Epub 2016 Jan 6.
MicroRNAs are highly conserved noncoding RNA that negatively modulate protein expression at a posttranscriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. To date, the potential microRNAs regulating the growth and progression of osteosarcoma are not fully identified yet. Previous reports have shown differentially expressed miR-125b in osteosarcoma. However, the role of miR-125b in human osteosarcoma has not been totally illuminated. In this study, we have shown that miR-125b was downregulated in human osteosarcoma tissues compared to the adjacent tissues and effects as a tumor suppressor in vitro We found that stable overexpression of miR-125b in osteosarcoma cell lines U2OS and MG-63 inhibited cell proliferation, migration, and invasion. Our data also verified that Bcl-2 is the target of miR-125b. Meanwhile, we showed that Bcl-2 was inversely correlated with miR-125b in osteosarcoma tissues. More importantly, we proved that miR-125b increased the chemosensitivity of osteosarcoma cell lines to cisplatin by targeting Bcl-2. In conclusion, our data demonstrate that miR-125b is a tumor suppressor and support its potential application for the treatment of osteosarcoma in the future.
微小RNA是高度保守的非编码RNA,在转录后和/或翻译水平上对蛋白质表达进行负调控,并深度参与多种癌症的发病机制。迄今为止,调控骨肉瘤生长和进展的潜在微小RNA尚未完全明确。先前的报道显示骨肉瘤中miR-125b表达存在差异。然而,miR-125b在人类骨肉瘤中的作用尚未完全阐明。在本研究中,我们发现与相邻组织相比,miR-125b在人类骨肉瘤组织中表达下调,并且在体外具有肿瘤抑制作用。我们发现,在骨肉瘤细胞系U2OS和MG-63中稳定过表达miR-125b可抑制细胞增殖、迁移和侵袭。我们的数据还证实Bcl-2是miR-125b的靶标。同时,我们发现骨肉瘤组织中Bcl-2与miR-125b呈负相关。更重要的是,我们证明miR-125b通过靶向Bcl-2增加了骨肉瘤细胞系对顺铂的化疗敏感性。总之,我们的数据表明miR-125b是一种肿瘤抑制因子,并支持其未来在骨肉瘤治疗中的潜在应用。