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Current Cancer Drug Targets
ISSN (Print): 1568-0096
ISSN (Online): 1873-5576
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The miR-183/96/182 Cluster Regulates Oxidative Apoptosis and Sensitizes Cells to Chemotherapy in Gliomas

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Author(s): Hailin Tang, Yanhui Bian, Chaofeng Tu, Zeyou Wang, Zhibin Yu, Qing Liu, Gang Xu, Minghua Wu and Guiyuan Li
Pages 1-11 (11)
Abstract:
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.
Keywords:
Glioma, micoRNA, miR-183, miR-182, miR-96, AKT, P53, Temozolomide, Apoptosis, Mitochondrial membrane potential
Affiliation:
Cancer Research Institute, Central South University, Changsha 410008, Hunan, P.R. China