Effect of HPV 16 E6 Oncoprotein Variants on the Alterations of the Proteome of C33A Cells

Background/Aim: The E6 genotypic variants of HPV 16 identified in lesions of women with cervical cancer (CC) in Southern Mexico include the E-G350, AAa, AAc, EC188/G350, and E-A176/G350. Transcriptomic analysis cells transfected with those variants showed to induce differential expression of the host genes involved in the development of CC. The aim of this work was to understand how the over-expression of the E6 oncoprotein and its variants can induce molecular mechanisms that lead to more aggressive HPV 16 phenotypes in cervical cancer and which proteins could be associated with the process. Materials and Methods: Total extracts from C33A, C33A mock, C33A AAa, C33A E-C188/G350, C33A E-A176/G350, and C33A E-prototype cells were analyzed using 2D electrophoresis, PDQuest software and mass spectrometry. Validation of results was performed through qPCR. Results: Statistically significant differential expression of 122 spots was detected, 12 of the identified proteins were associated with metabolism and metabolic programming. Out of these CCT8, ENO and ALDH1A were further validated. Conclusion: CCT8 and ALDH1A were found to be over-expressed in C33A AAa and C33A E-A176/G350, compared to the E prototype. Both proteins could be associated with a most aggressive phenotype due to their relationship with metabolism, protein folding and stemness, mechanisms associated to E6 that could be useful in the design of new therapies.

Automated summary

The study identified significant differential expression of 122 spots in cells transfected with different HPV 16 E6 genotypic variants, where 12 proteins related to metabolism and metabolic programming were found, among which CCT8, ENO, and ALDH1A were further validated. These proteins may play a role in more aggressive phenotypes associated with the E6 oncoprotein variants and could potentially be targeted for new therapeutic approaches.