Journal Article

miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma

Zhaohui Luo, Yafei Dai, Liyang zhang, Chen Jiang, Zheng Li, Jianbo Yang, James B. McCarthy, Xiaoling She, Wenling Zhang, Jian Ma, Wei Xiong, Minghua Wu, Jianhong Lu, Xiayu Li, Xiaoling Li, Juanjuan Xiang and Guiyuan Li

in Carcinogenesis

Volume 34, issue 2, pages 415-425
Published in print February 2013 | ISSN: 0143-3334
Published online October 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs329
miR-18a promotes malignant progression by impairing microRNA biogenesis  in nasopharyngeal carcinoma

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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.

Journal Article.  8486 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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