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Arrest of Cancer Cell Proliferation by dsRNAs
Author(s) -
KABILOVA TATYANA O.,
VLADIMIROVA AL`BINA V.,
CHERNOLOVSKAYA ELENA L.,
VLASSOV VALENTIN V.
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1378.085
Subject(s) - exon , microbiology and biotechnology , gene , rna interference , messenger rna , cell growth , biology , gene expression , intron , rna , interferon , cell culture , small interfering rna , chemistry , virology , genetics
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 β ‐actin .