398714 Targeting Key Genes of Cervical Carcinogenesis in Cancer Cell Lines Via siRNA

Monday, November 17, 2014
Galleria Exhibit Hall (Hilton Atlanta)
Khiem Lam1,2, Oleh Taratula1 and Andriy Morgun1, (1)College of Pharmacy, Oregon State University, Corvallis, OR, (2)School of Chemical, Biological, and Environmental Engineering, Oregon State University, Corvallis, OR

Cervical cancer is the second most common cancer among women worldwide with approximately 12,340 invasive cases diagnosed in 2013, in the U.S. alone. Unfortunately, even considering the anti-HPV vaccine related reduction to morbidity, cervical cancer will remain among the 10 most frequent cancers in women. Furthermore, the high mortality rate of cervical cancer patients (30% in the first five years) is attributed to the ineffectiveness of conventional therapeutic treatments. Thus, it is clear that a new and efficient therapeutic approach is highly warranted. It was recently proposed that simultaneously targeting of different carcinogenic pathways can be a promising therapeutic strategy that also prevents drug resistance. Moreover, it was shown that effective cancer treatment can be achieved by targeting genetic alterations of a given tumor harbored by individual patients. In a recent study, meta-analysis of genomic aberrations and global gene expression revealed key genes of cervical carcinogenesis, located in regions of chromosomal gains. It is hypothesized that blocking the expression of these key gene-drivers will result in the inhibition of tumor growth and metastatic activity. For this study, cervical cancer cell lines were transfected with the siRNA of key genes and in vitro assays were performed to evaluate different oncogenic pathways and expression of genes regulated by the key driver genes. Four genes (DUSP12, CKS1B, LAMP3, and RFC4) were chosen for initial testing in HeLa and ME180 cell lines that have chromosomal gains in the 1q and 3q region respectively. Cell viability results reveal that suppression of individual genes does not inhibit the growth of cancer cells dramatically. However, gene expression data does reveal co-regulation between specific genes which verifies the inferred networks of cervical cancer carcinogenesis. It is believed that combinations of siRNAs, targeted toward different key genes, will be able to achieve a larger effect on cancer growth and metastasis and at the very least, increase the susceptibility of cancer cells to other forms of treatment such as chemotherapy drugs. This conclusion is supported by cell viability and gene expression data, as well as other preliminary studies.

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