title: Expression of mitochondrial non-coding RNAs (ncRNAs) is modulated by high risk human papillomavirus (HPV) oncogenes.
abstract: The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.
authors.affiliation: Andes Biotechnologies SA, Fundación Ciencia para la Vida, Zanartu 1482 7782272, Chile. claudio.villota@gmail.com
authors.forename: Claudio
authors.initials: C
authors.lastname: Villota
authors.forename: América
authors.initials: A
authors.lastname: Campos
authors.forename: Soledad
authors.initials: S
authors.lastname: Vidaurre
authors.forename: Luciana
authors.initials: L
authors.lastname: Oliveira-Cruz
authors.forename: Enrique
authors.initials: E
authors.lastname: Boccardo
authors.forename: Verónica A
authors.initials: VA
authors.lastname: Burzio
authors.forename: Manuel
authors.initials: M
authors.lastname: Varas
authors.forename: Jaime
authors.initials: J
authors.lastname: Villegas
authors.forename: Luisa L
authors.initials: LL
authors.lastname: Villa
authors.forename: Pablo D T
authors.initials: PD
authors.lastname: Valenzuela
authors.forename: Miguel
authors.initials: M
authors.lastname: Socías
authors.forename: Sally
authors.initials: S
authors.lastname: Roberts
authors.forename: Luis O
authors.initials: LO
authors.lastname: Burzio
mesh_terms: D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D052161:Human papillomavirus 18 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis* / Q000235:genetics; D016372:RNA, Antisense / Q000096:biosynthesis* / Q000235:genetics; D000077278:RNA, Mitochondrial; D022661:RNA, Untranslated / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D009856:Oncogene Proteins, Viral; D016372:RNA, Antisense; D000077278:RNA, Mitochondrial; D022661:RNA, Untranslated; D012313:RNA