Caracterización in silico y molecular del LncRNA MINCR y su posible papel en la migración en células C33-A/AA-c de E6 del VPH-16.

Abstract

Infection with human papillomavirus 16 (HPV-16) is one of the first events in the carcinogenesis process in cervical cancer (CC). The expression of the viral oncoprotein E6 and E7 is essential in this process to inactivate the tumor suppressor proteins p53 and pRb, respectively, in addition to their interactions with other cellular proteins. Long noncoding RNAs (lncRNAs) have been found deregulated in various types of cancer, suggesting an important role in tumorigenesis. In this work, we analyzed the expression of the LncRNA MINCR in HPV-16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350 and E-G350) C33-A cells. We found that the expression of E6 oncoprotein positively regulates MINCR. Interestingly, the E6 variant E-C188/G350 increased the MINCR expression for 40 times, followed by the E6 variant AA-c with 9 times compared to the control. Through bioinformatic analysis, we determined that SP1 and MYC transcription factors could modulate the MINCR expression by an HPV-16 E6- dependent pathway. Additionally, it was predicted that MINCR targets five miRNAs and 119 mRNAs, which participate in cellular processes such as proliferation, migration, cell cycle and apoptosis. Our results suggest a possible lncRNA-microRNAs-mRNAs regulation axis in the migration of C33-A/AA-c cells.