Arrest of cancer cell proliferation by dsRNAs.
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.
Kabilova
Tatyana O
TO
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch-Russian Academy of Sciences, Lavrentiev Avenue 8, Novosibirsk 630090, Russia.
Vladimirova
Al 'Bina V
A'
Chernolovskaya
Elena L
EL
Vlassov
Valentin V
VV
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D020868:Gene Silencing; D006131:Growth Inhibitors / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D012330:RNA, Double-Stranded / Q000627:therapeutic use*; D034741:RNA, Small Interfering / Q000627:therapeutic use*
D006131:Growth Inhibitors; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering