Specific inhibition of gene expression and transactivation functions of hepatitis B virus X protein and c‐myc by small interfering RNAs

FEBS Letters

Hung, Le¹  Kumar, Vijay¹ 

[1] Virology Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India

关键词: Hepatitis B virus X protein;    Transactivation;    RNA interference;    Hepatocellular carcinoma;    Chloramphenicol acetyltransferase assay;    CAT;    chloramphenicol acetyltransferase;    HBx;    hepatitis B virus X protein;    dsRNA;    double-stranded RNA;    RNAi;    RNA interference;    shRNA;    small hairpin RNA;    siRNA;    small interfering RNA;   

DOI  :  10.1016/S0014-5793(04)00113-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

With a view to developing therapeutic strategies against hepatocellular carcinoma (HCC), we have recently shown that co-expression of c-myc and the X protein of hepatitis B virus (HBx) resulted in the development of HCC in the X-myc transgenic mice [Lakhtakia et al., J. Gastroenterol. Hepatol. 18 (2003) 80–91]. We now show in cell culture-based studies that small interfering RNA (siRNA) corresponding to HBx and c-myc can regulate expression and transactivation of the target genes. Expression vectors for small hairpin RNAs (shRNAs) against two different regions each of the HBx and c-myc open reading frames were constructed and their regulatory effects were investigated in COS-1 cells. A dose-dependent specific inhibition in the expression levels of HBx and c-myc was observed with individual shRNAs. Further, the recombinantly expressed shRNAs also blocked the transactivation functions of their cognate genes. Though each shRNA worked at a different efficiency, the inhibitory effects with two different shRNAs were cumulative. These results appear promising for developing a siRNA-based therapy for HCC.

【 授权许可】

Unknown