1. miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma.
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Luo, Zhaohui, Dai, Yafei, zhang, Liyang, Jiang, Chen, Li, Zheng, Yang, Jianbo, McCarthy, James B., She, Xiaoling, Zhang, Wenling, Ma, Jian, Xiong, Wei, Wu, Minghua, Lu, Jianhong, Li, Xiayu, Li, Xiaoling, Xiang, Juanjuan, and Li, Guiyuan
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MICRORNA , *CANCER invasiveness , *NASOPHARYNX cancer , *RIBONUCLEASES , *DNA microarrays , *NON-coding RNA , *EPSTEIN-Barr virus , *CADHERINS , *CANCER treatment - Abstract
Dysregulation of microRNA (miRNA) biogenesis is implicated in cancer development and progression. Dicer and Drosha are established regulators of miRNA biogenesis. In this study, we used a miRNA array to evaluate the miRNA expression profiles in nasopharyngeal carcinoma (NPC) samples. The significance analysis of microarrays showed a global downregulation of miRNA expression in NPC samples compared with normal nasopharyngeal epithelial tissues. Notably, miR-18a, a member of the oncogenic miR-17–92 cluster, was upregulated in the NPC samples and ell lines. Clinical parameter studies showed that higher levels of miR-18a correlated with NPC advanced stage, lymph node metastasis, Epstein-Barr virus infection and a higher death rate from NPC, indicating oncogenic roles in NPC development. The expression levels of miR-18a and Dicer1 were inversely related in NPC tissues. Further studies demonstrated that miR-18a negatively regulated Dicer1 by binding to the 3′ untranslated regions of Dicer1. In vitro and in vivo biological function assays showed that miR-18a promoted the growth, migration and invasion of NPC cells by regulating Dicer1 expression, which caused the global downregulation of miRNA expression levels including miR-200 family and miR-143. Furthermore, we found that the epithelial mesenchymal transition marker E-cadherin and the oncogene K-Ras were aberrantly expressed after miR-18a transduction, and these alterations were directly induced by downregulation of the miR-200 family and miR-143. Collectively, our findings indicate that miR-18a plays an oncogenic role in the development of NPC by widespread downregulation of the miRNome and could be a potential therapeutic target for NPC. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
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