HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes

Claudio Villota, Manuel Varas-Godoy, Emanuel Jeldes, América Campos, Jaime Villegas, Vincenzo Borgna, Luis O. Burzio, Verónica A. Burzio

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)33-47
Number of pages15
JournalAging
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Cervical cancer
  • Garrest
  • HPV-18 E2
  • Mitochondrial ncRNAs
  • Senescence

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

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