Suppression of E6 Oncogene Induces Apoptosis in CaSki Cervical Cancer Cells

Rasi, Farnaz; Zarredar, Habib; Amini, Mohammad; Onsori, Habib; Dadashzadeh, Kianoosh; Khanmohammadi, Majid; Vahedi, Leila; Mokhtarzadeh, Ahad; Baradaran, Behzad; Bannazadeh Baghi, Hossein

doi:10.31557/APJCP.2023.24.10.3389

Suppression of E6 Oncogene Induces Apoptosis in CaSki Cervical Cancer Cells

Document Type : Research Articles

Authors

¹ Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

² Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

³ Department of Biology Sciences, Marand Branch, Islamic Azad University, Marand, Iran.

⁴ Department of Laboratory Sciences, Marand Branch, Islamic Azad University, Marand, Iran.

⁵ Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

⁶ Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

⁷ Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

⁸ Department of Virology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

10.31557/APJCP.2023.24.10.3389

Abstract

Objective: The most important casuse of cervical cancer incidence and high mortality rate is infection to the human papillomavirus (HPV). The aim of the present study was to investigate the effect of silencing HPV E6 oncogene on cervical cancer cells using specific siRNAs. Materials and Methods: CaSki cervical cancer cells, carrying E6 gene, were cultured and then transfected with E6 targeting siRNAs. The cell viability through suppression of E6 expression was explored using MTT assay. Besides, apoptosis induction was investigated by means of flow cytometry using Annexin / PI staining. The changes in the expression of target genes were examined via Real-Time PCR. Results: E6 gene silencing caused a significant decrease in the survival rate of CaSki cells through remarkable enhancement of apoptosis induction. Moreover, E6 suppression led to significant upregulation of P53, Bax, Caspase-3, and Caspase-9 mRNA expression while downregulated Bcl-2 expression. Interestingly, it was found that suppression of E6 expression could lead to upregulation of E5 and E7 expression as a compensatory mechanism for E6 deactivation. Conclusion: According to the results of this study, suppression of E6 expression using specific siRNAs could be considered as a therapeutic approach for cervical cancer.

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