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

Resultado de la investigación: Article

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)33-47
Número de páginas15
PublicaciónAging
Volumen11
N.º1
DOI
EstadoPublished - 1 ene 2019

Huella dactilar

Antisense RNA
Untranslated RNA
Cell Aging
Keratinocytes
Down-Regulation
Human papillomavirus 18
Foreskin
Neoplasms
Human papillomavirus 16
HeLa Cells
Population
oncogene protein E2, Human papillomavirus type 18
mitochondrial RNA
Carcinogenesis
Proteins
Up-Regulation
Cell Proliferation
Phenotype

ASJC Scopus subject areas

  • Ageing
  • Cell Biology

Citar esto

Villota, Claudio ; Varas-Godoy, Manuel ; Jeldes, Emanuel ; Campos, América ; Villegas, Jaime ; Borgna, Vincenzo ; Burzio, Luis O. ; Burzio, Verónica A. / HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes. En: Aging. 2019 ; Vol. 11, N.º 1. pp. 33-47.
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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.",
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HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes. / Villota, Claudio; Varas-Godoy, Manuel; Jeldes, Emanuel; Campos, América; Villegas, Jaime; Borgna, Vincenzo; Burzio, Luis O.; Burzio, Verónica A.

En: Aging, Vol. 11, N.º 1, 01.01.2019, p. 33-47.

Resultado de la investigación: Article

TY - JOUR

T1 - HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes

AU - Villota, Claudio

AU - Varas-Godoy, Manuel

AU - Jeldes, Emanuel

AU - Campos, América

AU - Villegas, Jaime

AU - Borgna, Vincenzo

AU - Burzio, Luis O.

AU - Burzio, Verónica A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Cervical cancer

KW - Garrest

KW - HPV-18 E2

KW - Mitochondrial ncRNAs

KW - Senescence

UR - http://www.scopus.com/inward/record.url?scp=85060021295&partnerID=8YFLogxK

U2 - 10.18632/aging.101711

DO - 10.18632/aging.101711

M3 - Article

VL - 11

SP - 33

EP - 47

JO - Aging

JF - Aging

SN - 1945-4589

IS - 1

ER -