Down-regulation of miR-106b suppresses the growth of human glioma cells
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LABORATORY INVESTIGATION
Down-regulation of miR-106b suppresses the growth of human glioma cells Anling Zhang • Jianwei Hao • Kun Wang • Qiang Huang • Kai Yu • Chunsheng Kang • Guangxiu Wang • Zhifan Jia • Lei Han • Peiyu Pu
Received: 2 August 2012 / Accepted: 22 January 2013 / Published online: 2 February 2013 Ó Springer Science+Business Media New York 2013
Abstract Recently, many studies have found that the miR-106b *25 cluster plays an oncogenic role in tumor progression. However, the precise role of each microRNAs (miRNAs) in the cluster is not yet clear. In the present study, we examined the expression of miR-106b in glioma samples and a tissue microarray by real-time PCR and in situ hybridization (ISH), respectively, finding that miR106b is overexpressed in the majority of gliomas. Meanwhile, the expression of miR-106b was positively correlated with tumor grade (p \ 0.05). The transfection of a miR-106b anti-sense oligonucleotide (ASON) into three human glioma cell lines (U251, LN229 and TJ905) suppressed the proliferation of these cells. Moreover, the growth of xenograft tumors in nude mice treated with miR106b ASON was significantly impaired. A bioinformatics analysis predicted that RBL2 may be the target of miR106b, and dual-luciferase reporter assays identified RBL2, but not RB1 or RBL1, as a target of miR-106b. These results suggest that miR-106b facilitates glioma cell growth
Electronic supplementary material The online version of this article (doi:10.1007/s11060-013-1061-2) contains supplementary material, which is available to authorized users. A. Zhang J. Hao K. Wang Q. Huang K. Yu C. Kang G. Wang Z. Jia L. Han P. Pu (&) Department of Neurosurgery; Tianjin Medical University General Hospital; Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration of the Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of the Nervous System, 154 Anshan Road, Heping District, Tianjin 300052, People’s Republic of China e-mail: [email protected]; [email protected]
by promoting cell cycle progression through the negative regulation of RBL2. Keywords Glioma miR-106b Expression miR-106b ASON RBL2
Introduction Gliomas are the most common type of primary central nervous system tumors. The overall worldwide incidence of primary malignant brain and central nervous system tumors was 6.3 per 100,000 persons in 2002 [1, 2]. The 5-year survival rate of patients with glioblastomas (GBM) is less than 10 % [3]. A more precise understanding of the molecular pathogenesis of glioma formation and progression is necessary for the development and optimization of glioma treatment strategies. MicroRNAs (miRNAs) are small endogenous non-coding single-stranded RNAs that can interfere with protein expression by either inducing the cleavage of a specific target mRNAs or by inhibiting the translation of target mRNAs [4]. To date, scientists have identified a total of 15,172 miRNAs in various species such as animals, pla
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