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

J Cancer Res Clin Oncol. 2011 Mar;137(3):415-22. doi: 10.1007/s00432-010-0898-4. Epub 2010 May 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • MicroRNAs / genetics*
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology
  • Proto-Oncogene Proteins c-myc / biosynthesis
  • Proto-Oncogene Proteins c-myc / genetics*
  • Transfection
  • Up-Regulation / drug effects


  • MYC protein, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • mirnlet7 microRNA, human
  • Cytidine
  • pyrimidin-2-one beta-ribofuranoside
  • Azacitidine