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.

• Carolina E. Vaisman, Oscar Del Moral-Hernandez, Samadhi Moreno-Campuzano, Elena Aréchaga-Ocampo, Raul Bonilla-Moreno, Israel Garcia-Aguiar, Leticia Cedillo-Barron, Jaime Berumen, Porfirio Nava and Nicolas Villegas-Sepúlveda C33-A cells transfected with E6*I or E6*II the short forms of HPV-16 E6, displayed opposite effects on cisplatin-induced apoptosis”Virus research.

• Martinez-Castillo M, Bonilla-Moreno R, Aleman-Lazarini L, Meraz-Rios MA, Orozco L, Cedillo-Barron L, Cordova EJ, Villegas-Sepulveda N. A Subpopulation of the K562 Cells Are Killed by Curcumin Treatment after G2/M Arrest and Mitotic Catastrophe. PLoS One. 2016 Nov 10;11(11):e0165971. doi: 10.1371/journal.pone.0165971.

• del Moral-Hernández O, López-Urrutia E, Bonilla-Moreno R, Martínez-Salazar M, Arechaga-Ocampo E, Berumen J, Villegas-Sepúlveda N. The HPV-16 E7 oncoprotein is expressed mainly from the unspliced E6/E7 transcript in cervical carcinoma C33-A cells. Arch Virol. 2010 Dec;155(12):1959-70. Epub 2010 Sep

• Aréchaga-Ocampo E, Pereira-Suárez AL, del Moral-Hernández O, Cedillo-Barrón L, Rodríguez-Sastre MA, Castillo-Alvarez A, López-Bayghen E, Villegas-Sepúlveda N. HPV+ cervical carcinomas and cell lines display altered expression of caspases. Gynecol Oncol. 2008 Jan;108(1):10-8.

• De la Rosa-Rios MA, Martínez-Salazar M, Martínez-Garcia M, González-Bonilla C, Villegas-Sepúlveda N. The intron 1 of HPV 16 has a suboptimal branch point at a guanosine. Virus Res. 2006 Jun;118(1-2):46-54. Epub 2005 Dec 15

Publications http://www.ncbi.nlm.nih.gov/sites/myncbi/collections/public/1Lo0oAdCWmdJBWddIxuwibHAf/?sort=date&direction=descending