10.6084/m9.figshare.4285256.v1
Chin-Yo Lin
Chin-Yo
Lin
Erica L. Kleinbrink
Erica L.
Kleinbrink
Fabien Dachet
Fabien
Dachet
Juan Cai
Juan
Cai
Donghong Ju
Donghong
Ju
Amanda Goldstone
Amanda
Goldstone
Emily J. Wood
Emily J.
Wood
Ka Liu
Ka
Liu
Hui Jia
Hui
Jia
Anton-Scott Goustin
Anton-Scott
Goustin
Mary A. Kosir
Mary A.
Kosir
Pattaraporn Thepsuwan
Pattaraporn
Thepsuwan
Leonard Lipovich
Leonard
Lipovich
ENCODE Gingeras from Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells
The Royal Society
2016
oestrogen
long non-coding RNA
map kinase
evolution
cancer
2016-12-05 11:39:14
Journal contribution
https://rs.figshare.com/articles/journal_contribution/ENCODE_Gingeras_from_Primate-specific_oestrogen-responsive_long_non-coding_RNAs_regulate_proliferation_and_viability_of_human_breast_cancer_cells/4285256
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.