The use of ribonucleic acid interference (RNAi) technology for IQGAPS gene as target for treatment of hepato-cellular carcinoma


General Information

12- BIO2926-02

The use of ribonucleic acid interference (RNAi) technology for IQGAPS gene as target for treatment of hepato-cellular carcinoma

Biotechnology

Disease molecular diagnosis

Hepatocellular carcinoma (HCC) is responsible for between 500,000 and 1 million worldwide deaths annually. HCC etiologies are diverse and include chronic hepatitis B (HBV) and C (HCV), chronic excessive alcohol consumption, steatosis, diabetes, and exposure to toxic agents such as aflatoxin B1, or any hepatic disease associated with cirrhosis IQ-domain GTPase-activating proteins (IQGAPs) are an evolutionary conserved family of multi-domain proteins that regulate distinct cellular processes. IQGAP1 is ubiquitously expressed, while IQGAP2 and IQGAP3 are mainly restricted to liver. There is mounting evidence to suggest a role for IQGAP1 in cancer progression while IQGAP2 may be a tumor suppressor. Ribonucleic acid interference (RNAi) technologies are already widely used as a tool for reverse genetics in mammalian cells and their potential therapeutic applications are likely to come in the future. One exciting application has been the use of small interference RNA (siRNA) based gene silencing technologies in the inhibition of viral replication and infection. This project will focus on the study of genetic structure of the different types of IQGAPs genes (IQGAP1, IQGAP 2 and IQGAP 3). Study the expression level in different types of cells (normal hepatic cells, HCC (in vivo). This will be done using real time PCR, western and eastern blot and ELISA technologies. To confirm or cancel the hypothesis that suggests that IQGAP2 may be a tumor suppressor and IQGAP1 is an oncogene and describe the rule of IQGAP3 gene. Depending on our findings we will use RNAi technology to silencing for IQGAP oncogene to prevent completely or partially hepatic cancer by designing short RNAi specific for IQGAP gene for the different types of HCC cells in vivo and in vitro and construct new vectors suitable for this purpose.

First Goal, The cumulative evidence suggests IQGAP1 is an oncogene while IQGAP2 may be a tumor suppressor so our study will focus in the beginning on the study of genetic structure of the different types of IQGAPs genes (IQGAP1, IQGAP 2 and IQGAP 3) as follow: Study the expression level in different types of cells (normal hepatic cells, HCC (in vivo) by using real time PCR, western and eastern blot and ELISA technologies to confirm or cancel the hypothesis that suggests that IQGAP2 may be a tumor suppressor and IQGAP1 is an oncogene and try to find and describe the rule of IQGAP3 gene. Determine the homology and heterology of IQGAPs genetic structures in the different types of cells by using mitochondrial DNA assay and DNA sequencing to study the mutation points that occur in these genes. Second Goal of The Project, Depending on our findings and the genetic structure of IQGAPs we will use RNAi technology to make inhibition or silencing for IQGAP oncogene to prevent completely or partially hepatic cancer by designing short RNAi specific for IQGAP gene for the different types of HCC cells in vivo and in vitro and construct new vectors suitable for this purposes. Study the effect of RNAi injection on cell apoptosis and genes expression of different types of genes.

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