Supplementary material from "Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells"
Posted on 2016-12-05 - 11:40
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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Lin, Chin-Yo; Kleinbrink, Erica L.; Dachet, Fabien; Cai, Juan; Ju, Donghong; Goldstone, Amanda; et al. (2016). Supplementary material from "Primate-specific oestrogen-responsive long non-coding RNAs regulate proliferation and viability of human breast cancer cells". The Royal Society. Collection. https://doi.org/10.6084/m9.figshare.c.3588716.v1
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AUTHORS (13)
CL
Chin-Yo Lin
EK
Erica L. Kleinbrink
FD
Fabien Dachet
JC
Juan Cai
DJ
Donghong Ju
AG
Amanda Goldstone
EW
Emily J. Wood
KL
Ka Liu
HJ
Hui Jia
AG
Anton-Scott Goustin
MK
Mary A. Kosir
PT
Pattaraporn Thepsuwan
LL
Leonard Lipovich