Research Paper Volume 11, Issue 1 pp 33—47
HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes
- 1 Fundación Ciencia & Vida, Santiago, Chile
- 2 Andes Biotechnologies SpA, Santiago, Chile
- 3 Departamento de Ciencias Químicas y Biológicas, Facultad de Salud, Universidad Bernardo O’Higgins, Santiago, Chile
- 4 Centro de Investigación Biomédica, Facultad de Medicina, Universidad de los Andes, Santiago, Chile
- 5 Departamento de Ciencias Biológicas, Facultad de Ciencias de la Vida, Universidad Andrés Bello, Santiago, Chile
- 6 Laboratorio de Comunicaciones Celulares (CEMC) Facultad de Medicina, Universidad de Chile, Santiago, Chile
- 7 Faculty of Medical Sciences, Universidad de Santiago de Chile, Santiago, Chile
received: July 27, 2018 ; accepted: December 6, 2018 ; published: December 30, 2018 ;https://doi.org/10.18632/aging.101711
How to Cite
Copyright: Villota et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Human and mouse cells display a differential expression pattern of a family of mitochondrial noncoding RNAs (ncmtRNAs), according to proliferative status. Normal proliferating and cancer cells express a sense ncmtRNA (SncmtRNA), which seems to be required for cell proliferation, and two antisense transcripts referred to as ASncmtRNA-1 and -2. Remarkably however, the ASncmtRNAs are downregulated in human and mouse cancer cells, including HeLa and SiHa cells, transformed with HPV-18 and HPV-16, respectively. HPV E2 protein is considered a tumor suppressor in the context of high-risk HPV-induced transformation and therefore, to explore the mechanisms involved in the downregulation of ASncmtRNAs during tumorigenesis, we studied human foreskin keratinocytes (HFK) transduced with lentiviral-encoded HPV-18 E2. Transduced cells displayed a significantly extended replicative lifespan of up to 23 population doublings, compared to 8 in control cells, together with downregulation of the ASncmtRNAs. At 26 population doublings, cells transduced with E2 were arrested at G2/M, together with downregulation of E2 and SncmtRNA and upregulation of ASncmtRNA-2. Our results suggest a role for high-risk HPV E2 protein in cellular immortalization. Additionally, we propose a new cellular phenotype according to the expression of the SncmtRNA and the ASncmtRNAs.