Zhang Jie, Wu Weining, Xu Shuo, Zhang Jian, Zhang Jiale, Yu Qun, Jiao Yuanyuan, Wang Yingyi, Lu Ailin, You Yongping, Zhang Junxia, Lu Xiaoming
1 Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
2 Department of Hematology, Shengjing Hospital Affiliated to China Medical University, Shenyang, People's Republic of China.
Tumour Biol. 2017 Jun;39(6):1010428317705766. doi: 10.1177/1010428317705766.
Glioma accounts for the majority of primary malignant brain tumors in adults and is highly aggressive. Although various therapeutic approaches have been applied, outcomes of glioma treatment remain poor. MicroRNAs are a class of small noncoding RNAs that function as regulators of gene expression. Accumulating evidence shows that microRNAs are associated with tumorigenesis and tumor progression. In this study, we found that miR-105 is significantly downregulated in glioma tissues and glioma cell lines. We identified suppressor of Zeste 12 homolog as a novel direct target of miR-105 and showed that suppressor of Zeste 12 homolog protein levels were inversely correlated with the levels of miR-105 expression in clinical specimens. Overexpression of miR-105 inhibited cell proliferation, tumorigenesis, migration, invasion, and drug sensitivity, whereas overexpression of suppressor of Zeste 12 homolog antagonized the tumor-suppressive functions of miR-105. Taken together, our results indicate that miR-105 plays a significant role in tumor behavior and malignant progression, which may provide a novel therapeutic strategy for the treatment of glioma and other cancers.
胶质瘤占成人原发性恶性脑肿瘤的大多数,且具有高度侵袭性。尽管已应用了各种治疗方法,但胶质瘤的治疗效果仍然很差。微小RNA是一类作为基因表达调节因子的小型非编码RNA。越来越多的证据表明,微小RNA与肿瘤发生和肿瘤进展相关。在本研究中,我们发现miR-105在胶质瘤组织和胶质瘤细胞系中显著下调。我们确定Zeste 12同源物抑制因子是miR-105的一个新的直接靶点,并表明在临床标本中,Zeste 12同源物抑制因子的蛋白水平与miR-105的表达水平呈负相关。miR-105的过表达抑制细胞增殖、肿瘤发生、迁移、侵袭和药物敏感性,而Zeste 12同源物抑制因子的过表达则拮抗miR-105的肿瘤抑制功能。综上所述,我们的结果表明miR-105在肿瘤行为和恶性进展中起重要作用,这可能为胶质瘤和其他癌症的治疗提供一种新的治疗策略。