Zhou Zhenhua, Wang Zhiwei, Wei Haifeng, Wu Sujia, Wang Xudong, Xiao Jianru
Department of Orthopaedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China Department of Orthopaedics, 169th Hospital of PLA, Hengyang, Hunan, China Department of Orthopaedics, Xiangnan Hospital, College of Medicine, Hunan Normal University, Hengyang, Hunan, China.
Department of Orthopaedics, Changhai Hospital, Second Military Medical University, Shanghai, China.
Clin Sci (Lond). 2016 Jun 1;130(11):921-30. doi: 10.1042/CS20150509. Epub 2016 Mar 18.
MicroRNAs play important roles in the development of cancers. Although miR-92b has been reported to promote the tumorigenesis of some cancers, its role in osteosarcoma remains unknown. In the present study, we focused on the expression, function and mechanisms of miR-92b in osteosarcoma development. The miRNA miR-92b was up-regulated in osteosarcoma cell lines and tissues; miR-92b up-regulation correlated with poor prognosis in osteosarcoma. Overexpression of miR-92b promoted osteosarcoma cell proliferation, migration and invasion, which was abrogated by miR-92b inhibition. Reversion-inducing, cysteine-rich protein with kazal motifs (RECK) was identified as the direct and functional target of miR-92b in osteosarcoma. Importantly, restoring RECK expression abrogated increases in cell growth, motility and invasiveness induced by miR-92b RECK was down-regulated in osteosarcoma tissues, and its expression level negatively correlated with miR-92b Collectively, our results indicate that miR-92b acts as an oncogenic miRNA and may be a therapeutic target in osteosarcoma.
微小RNA在癌症发展过程中发挥着重要作用。尽管已有报道称miR-92b可促进某些癌症的肿瘤发生,但其在骨肉瘤中的作用仍不清楚。在本研究中,我们聚焦于miR-92b在骨肉瘤发展中的表达、功能及机制。miR-92b在骨肉瘤细胞系和组织中表达上调;miR-92b上调与骨肉瘤患者的不良预后相关。miR-92b过表达促进骨肉瘤细胞增殖、迁移和侵袭,而miR-92b抑制可消除这些作用。富含半胱氨酸的kazal基序逆转诱导蛋白(RECK)被确定为miR-92b在骨肉瘤中的直接功能性靶标。重要的是,恢复RECK表达可消除miR-92b诱导的细胞生长、运动和侵袭能力的增强。RECK在骨肉瘤组织中表达下调,其表达水平与miR-92b呈负相关。总体而言,我们的结果表明miR-92b作为一种致癌性微小RNA,可能是骨肉瘤的治疗靶点。