MiR-135a functions as a selective killer of malignant glioma

Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China.
Oncogene (Impact Factor: 8.46). 12/2011; 31(34):3866-74. DOI: 10.1038/onc.2011.551
Source: PubMed

ABSTRACT Glioma is the most common and fatal primary brain tumor. Thus far, therapeutic strategies to efficiently and specifically antagonize glioma are limited and poorly developed. Here we report that glia-enriched miR-135a, a microRNA that is dramatically downregulated in malignant glioma and correlated with the pathological grading, is capable of inducing mitochondria-dependent apoptosis of malignant glioma by regulating various genes including STAT6, SMAD5 and BMPR2, as well as affecting the signaling pathway downstream. Moreover, this lethal effect is selectively towards malignant glioma cells, but not neurons and glial cells, through a novel mechanism. Our findings suggest an important role of miR-135a in glioma etiology and provide a potential candidate for malignant glioma therapy.

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Available from: Sihan Wu, Jun 17, 2015
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    • "However, the functions of these miRNAs in the brain, especially in astrocytes, and how they are linked to the pathogenesis of neurodegeneration are unknown. miR135a is enriched in glial cells and has been shown to induce mitochondriadependent apoptosis in malignant glioma (Wu et al., 2012), but the function of miR135a in inflamed brains has not been explored. "
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    Neurobiology of Aging 12/2014; 36(3). DOI:10.1016/j.neurobiolaging.2014.11.020 · 5.01 Impact Factor
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    • "Over-expression of these miRNAs induced dissipation of ΔΨ m,i and the release of cytochrome c [104]. Furthermore, MiR-135a, considerably down-regulated in malignant gliomas and correlated with the pathological grading of the neoplasia, can induce mitochondriadependent apoptosis of malignant gliomas by regulating various genes including STAT6, SMAD5 and BMPR2, as well as affecting the downstream signalling events [105]. "
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    • "The human cervical carcinoma cell line HeLa was obtained from the China Center for Type Culture Collection (Wuhan, China). The human normal glial cell line HEB was kindly provided by Dr. Guangmei Yan (Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China) [36]. HeLa, A172 and U251 cells were maintained in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum (FBS), 5 mM L-glutamine, 100 U/ml penicillin and 100 mg/ml streptomycin. "
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