MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Wong
Thian-Sze
TS
Department of Surgery, Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China. thiansze@graduate.hku.hk
Man
On-Ying
OY
Tsang
Chi-Man
CM
Tsao
Sai-Wah
SW
Tsang
Ramond King-Yin
RK
Chan
Jimmy Yu-Wai
JY
Ho
Wai-Kuen
WK
Wei
William Ignace
WI
To
Victor Shing-Howe
VS
D001374:Azacitidine / Q000494:pharmacology; D002277:Carcinoma; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D003562:Cytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects
C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; C487931:mirnlet7 microRNA, human; D003562:Cytidine; C009131:pyrimidin-2-one beta-ribofuranoside; D001374:Azacitidine