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Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells.
Lin, Chin-Yo; Kleinbrink, Erica L; Dachet, Fabien; Cai, Juan; Ju, Donghong; Goldstone, Amanda; Wood, Emily J; Liu, Ka; Jia, Hui; Goustin, Anton-Scott; Kosir, Mary A; Thepsuwan, Pattaraporn; Lipovich, Leonard.
Afiliación
  • Lin CY; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, USA.
  • Kleinbrink EL; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Dachet F; Department of Neurology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
  • Cai J; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Ju D; Department of Neurology and Rehabilitation, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
  • Goldstone A; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Wood EJ; Department of Surgery and Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
  • Liu K; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Jia H; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Goustin AS; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77004, USA.
  • Kosir MA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Thepsuwan P; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
  • Lipovich L; Department of Surgery and Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
Open Biol ; 6(12)2016 12.
Article en En | MEDLINE | ID: mdl-28003470
Long non-coding RNAs (lncRNAs) are transcripts of a recently discovered class of genes which do not code for proteins. LncRNA genes are approximately as numerous as protein-coding genes in the human genome. However, comparatively little remains known about lncRNA functions. We globally interrogated changes in the lncRNA transcriptome of oestrogen receptor positive human breast cancer cells following treatment with oestrogen, and identified 127 oestrogen-responsive lncRNAs. Consistent with the emerging evidence that most human lncRNA genes lack homologues outside of primates, our evolutionary analysis revealed primate-specific lncRNAs downstream of oestrogen signalling. We demonstrate, using multiple functional assays to probe gain- and loss-of-function phenotypes in two oestrogen receptor positive human breast cancer cell lines, that two primate-specific oestrogen-responsive lncRNAs identified in this study (the oestrogen-repressed lncRNA BC041455, which reduces cell viability, and the oestrogen-induced lncRNA CR593775, which increases cell viability) exert previously unrecognized functions in cell proliferation and growth factor signalling pathways. The results suggest that oestrogen-responsive lncRNAs are capable of altering the proliferation and viability of human breast cancer cells. No effects on cellular phenotypes were associated with control transfections. As heretofore unappreciated components of key signalling pathways in cancers, including the MAP kinase pathway, lncRNAs hence represent a novel mechanism of action for oestrogen effects on cellular proliferation and viability phenotypes. This finding warrants further investigation in basic and translational studies of breast and potentially other types of cancers, has broad relevance to lncRNAs in other nuclear hormone receptor pathways, and should facilitate exploiting and targeting these cell viability modulating lncRNAs in post-genomic therapeutics.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Primates / Neoplasias de la Mama / Estrógenos / ARN Largo no Codificante Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Open Biol Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Primates / Neoplasias de la Mama / Estrógenos / ARN Largo no Codificante Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Open Biol Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido