The inhibitory effect of small interference RNA of Human papillomavirus type 16 E6/E7 oncogenes on transforming phenotypes of TC-1 tumor cell line

[[abstract]]Human papillomaviruses (HPV) are a family of small DNA viruses that have been linked to a variety of human diseases. The high-risk types of HPV, including HPV-16 and HPV-18, have been implicated in the causation and malignant progression of human cervical cancer. The consistent expression of two viral genes, E6 and E7, are required for the establishment and maintenance of a fully transformed phenotype. Therefore, the E6 and E7 genes can be considered relevant targets for anti-cancer therapy. Recently, a powerful reverse genetic tool termed small interfering RNA (siRNA) has been developed which can induce sequence-specific gene silencing through RNA-mediated interference (RNAi) in mammalian cells. this thesis, we demonstrated that synthetic siRNA targeted to various region of HPV-16 E6 and E7 mRNAs can specifically block the expression and function of respective viral oncogenes in HPV-positive TC-1 tumor cell lines. It is shown that siRNAs to E6 and E7 messages were useful in inhibiting cell growth and in reversing the transformed phenomena like anchorage-independency. These observations augurs well for the therapeutic potential of anti-E6 and anti-E7 siRNA in HPV-related cancers