RESUMO
Inhibition of c-myc and N-myc genes by dsRNAs in carcinoma and neuroblastoma cells was investigated. siRNA-Ex3 targeted to the third exon of c-myc gene was found to decrease the level of c-myc but not N-myc mRNA and decrease the rate or even arrest proliferation of c-myc overexpressing cell lines KB-3-1 and SK-N-MC. This siRNA did not affect proliferation of IMR-32 (which overexpress N-myc). siRNA-Ex2 corresponding (with 1-2 mismatches) to the conservative region of the second exon of both c- and N-myc was able to downregulate both genes and to reduce proliferation of KB-3-1, SK-N-MC, and IMR-32 cells. Long dsRNA corresponding to the 3 exon of c-myc gene (dsMyc), poly(I:C), and GU-rich siRNA-I, corresponding to the intron sequence of human MDR1 gene demonstrated high antiproliferative activity in experiments with KB-3-1 cells. Short-term elevation of PKR or/and OAS1 mRNA levels was detected in the cells affected by interferon inducer poly(I:C). dsMyc, poly(I:C), and even siRNA-I, which could not affect c-myc mRNA by RNA interference mechanism, were found to inhibit proliferation of the KB-3-1 cells and to decrease the mRNA level of interferon-sensitive genes c-myc and beta-actin.