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miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma.
- Source :
-
Carcinogenesis [Carcinogenesis] 2013 Feb; Vol. 34 (2), pp. 415-25. Date of Electronic Publication: 2012 Oct 24. - Publication Year :
- 2013
-
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 cell 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.
- Subjects :
- Animals
Biomarkers, Tumor metabolism
Blotting, Western
Carcinoma
Case-Control Studies
Cell Adhesion
Cell Movement
Cell Proliferation
Disease Progression
Female
Gene Expression Profiling
Humans
Immunoenzyme Techniques
In Situ Hybridization
Luciferases metabolism
Male
Mice
Mice, Nude
MicroRNAs antagonists & inhibitors
MicroRNAs genetics
Middle Aged
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms genetics
Nasopharyngeal Neoplasms mortality
Nasopharynx metabolism
Neoplasm Staging
Oligonucleotide Array Sequence Analysis
RNA, Messenger genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Survival Rate
Wound Healing
Apoptosis
Biomarkers, Tumor genetics
Gene Expression Regulation, Neoplastic
MicroRNAs physiology
Nasopharyngeal Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2180
- Volume :
- 34
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 23097559
- Full Text :
- https://doi.org/10.1093/carcin/bgs329