Suppression of DNA methyltransferase 1 levels in head and neck squamous carcinoma cells using small interfering RNA results in growth inhibition and increase in Cdk inhibitor p21.
The ectopic expression of DNA methyltransferase 1 (DNMT 1) can transforms mammalian cells, and the inhibition of DNMT1 activity reverses that phenotypic transformation. Therefore, DNMT1 is considered to be an excellent target for therapeutic intervention. Previously, inhibition of DNMT1 was accomplished by using an antagonist or by antisense oligonucleotides. In this study, we examined the ability of the novel approach using small interfering RNA (siRNA) to disrupt the expression of DNMT1 in human non-small cell lung carcinoma A549 cells and the consequences of such an intervention. Transfection of DNMT1 siRNA decreased DNMT1 protein levels specifically and effectively. This decrease was accompanied by suppression of cell proliferation and colony-forming ability. The mechanism of this inhibition may be related to the increased levels of the cyclin dependent kinase inhibitor p21. These results suggest that the siRNA approach can be used to disrupt effectively DNMT1 activity and cancer cell growth.
Oridate
Nobuhiko
N
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Lotan
Reuben
R
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis* / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000032:analysis* / Q000096:biosynthesis*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D010641:Phenotype; D034741:RNA, Small Interfering; D014162:Transfection
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human