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J Cancer Res Clin Oncol ; 137(3): 415-22, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20440510

ABSTRACT

AIMS: This study aimed at evaluating the potential anti-proliferative effects of the microRNA let-7 family in nasopharyngeal carcinoma (NPC) cells. In addition, the association between let-7 suppression and DNA hypermethylation is examined. MATERIALS AND METHODS: Levels of mature let-7 family members (-a, -b, -d, -e, -g, and -i) in normal nasopharyngeal cells (NP69 and NP460) and nasopharyngeal carcinoma cells (HK1 and HONE1) were measured by real-time quantitative PCR. Cell-proliferation assay and c-Myc immunohistochemical staining were performed on NPC cells transfected with let-7 precursor molecules. In addition, expression changes in let-7 family members in response to demethylating agents (5-azacytidine and zebularine) were also examined. RESULTS: In comparison with the normal nasopharyngeal cells, let-7 (-a, -b, -d, -e, -g, and -i) levels were reduced in nasopharyngeal carcinoma cells. Ectopic expression of the let-7 family in nasopharyngeal carcinoma cells resulted in inhibition of cell proliferation through downregulation of c-Myc expression. Demethylation treatment of nasopharyngeal carcinoma cells caused activation of let-7 expression in poorly differentiated nasopharyngeal carcinoma cells only. CONCLUSION: Our results suggested that miRNA let-7 might play a role in the proliferation of NPC. DNA methylation is a potential regulatory pathway, which is affected when let-7 is suppressed in NPC cells. However, the extent of DNA hypermethylation/hypomethylation in regulating let-7 expression requires further elucidation.


Subject(s)
MicroRNAs/genetics , Proto-Oncogene Proteins c-myc/genetics , Azacitidine/pharmacology , Carcinoma , Cell Growth Processes/genetics , Cell Line, Tumor , Cytidine/analogs & derivatives , Cytidine/pharmacology , DNA Methylation/drug effects , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/metabolism , Nasopharyngeal Neoplasms/pathology , Proto-Oncogene Proteins c-myc/biosynthesis , Transfection , Up-Regulation/drug effects
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