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Many microRNAs reside in clusters in the genome, are generally similar in sequence, are transcribed in the same direction, and usually function synergistically. The miR-183/96/182 cluster is composed of 3 miRNA genes, and increased expression of miR-183, 96 and 182 are implicated in glioma carcinogenesis. Knockdown of individual components or of the entire miR-183/96/182 cluster inhibits the survival of glioma cells by regulating the ROS-induced apoptosis pathway. Furthermore, inhibition of the miR-183/96/182 cluster induced ROS-mediated AKT/survival independent of three target genes FGF9, CPEB1, and FOXO1, and inhibition of the miRNA cluster induced p53/apoptosis signaling, which was dependent on these same genes. In addition, knockdown of the miR-183/96/182 cluster enhanced the anticancer effect of Temozolomide on glioma cells by the ROS-mediated apoptosis pathway. Therefore, the miR-183/96/182 cluster may be a pleiotropic target for glioma therapy.
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Tang et al. (2013) studied this question.
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