Oncogenic mechanisms in HPV-16 infected cells, using as model E6/E7 splicing, and its role in cervical cancer development.
State of art
High risk human papillomaviruses (hrHPV) are small DNA viruses that infect mucosal and epithelial tissues. Expression of the E6 and E7 oncoproteins from hrHPV induce cellular immortalization and transformation of keratinocyte cells. The E6/E7 genes from hrHPVs are processed by splicing mechanisms. The intron 1 from the E6/E7 genes of HPV-16 is processed by alternative splicing and its transcripts are detected whit a heterogeneous profile in tumors cells and tumor derived-cell lines. The heterogeneous profile of the E6/E7 transcripts depends in the variation of the expression level of some splicing factors in the host cells, and also in the sequence polymorphism of the viral variants of HPV-16. Although, the splicing factors involved in the regulation of the E6/E7 alternative splicing, are largely unknown. Likely, the heterogeneous profile of the E6/E7 spliced transcripts reflected the expression changes of some canonical and key accessory splicing factors involved in the regulation of HPV-16 alternative splicing. Variation in the expression of splicing factor is a common characteristic of cancer and leukemia cells. Additionally, the variation of expression of key splicing factors, it is likely involved in the global alterations of the transcriptome and proteome observed in many cancer cells. Whether HPV-16 infection contributes directly or indirectly in this splicing factor variegation in cervical carcinoma cells, and this phenomenon has a global effect in the expression of key components in the regulation of cell homeostasis, remains to be demonstrated.
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