June 15, 2009 A research group in China applied a DNA vector-based STAT3-specific RNA interfering approach to block STAT3 signaling and to evaluate the biological consequences of STAT3 down-modulation on tumor growth using a tumor-bearing nude mice model. Silencing of STAT3 by RNAi suppresses tumor growth in vivo and STAT3 may act as an effective target for HCC therapy.
It has been shown that constitutively activated STAT3 is detected in many HCC cell lines and tissues. This suggests that STAT3 is a promising molecular target for HCC gene therapy. RNA interference (RNAi) is a post-transcriptional gene-silencing mechanism, in which the homologous RNA sequences could be introduced into cells that inhibit the expression of a particular gene through the introduction of short interfering RNAs (siRNA). There were a large number of confirmed reports that RNAi targeting oncogene could successfully inhibit the growth of tumor cells in vitro and in vivo. Hence, RNAi has been turned into a potent technology for tumor therapy. Yet, there are no reports about targeting STAT3 by RNAi in HCC.
A research article to be published on June 7, 2009 in the World Journal of Gastroenterology addresses this question. The research team led by Professor Piao from Liaoning Medical University and Jinlin University applied a DNA vector-based STAT3-specific RNA interfering approach to block STAT3 signaling and to evaluate the biological consequences of STAT3 down-modulation on tumor growth using a tumor-bearing nude mice model.
The research revealed that silencing STAT3 by RNAi inhibited the growth of HCC cells in vivo, induced apoptosis, and had significant antineoplastic efficacy. RNAi that targets STAT3 has a clear therapeutic effect in HCC. Therefore, STAT3 may become an important target of biological therapy in HCC, which brings hope of clinical therapy using RNAi oligonucleotide drugs. It may also offer a theoretical and experimental foundation for the clinical application of synthetic dsRNA-based RNAi.
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- Li J, Piao YF, Jiang Z, Chen L, Sun HB. Silencing of signal transducer and activator of transcription 3 expression by RNA interference suppresses growth of human hepatocellular carcinoma in tumor-bearing nude mice. World Journal of Gastroenterology, 2009; 15 (21): 2602 DOI: 10.3748/wjg.15.2602
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