Open AccessSOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer
Author(s) -
Carole FerraroPeyret,
Marjan Askarian-Amiri,
Debina Sarkar,
Wayne R. Joseph,
Herah Hansji,
Bruce C. Baguley,
Euphemia Leung
Publication year - 2020
Publication title -
sci
Language(s) - English
Resource type - Journals
ISSN - 2413-4155
DOI - 10.3390/sci2020024
Subject(s) - tamoxifen , breast cancer , biology , cancer research , estrogen receptor , unfolded protein response , medicine , endocrinology , xbp1 , endoplasmic reticulum , cancer , rna , microbiology and biotechnology , gene , rna splicing , genetics
Endoplasmic reticulum (ER) stress perturbs cell homeostasis and induces the unfolded protein response (UPR). In breast cancer, this process is activated by oestrogen deprivation and is associated with tamoxifen resistance. We present evidence that the transcription factor SOX2 and the long noncoding RNA SOX2 overlapping transcript (SOX2OT) are up-regulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and SOX2OT expression, and the effect of SOX2OT on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation up-regulates SOX2OT expression. This up-regulation is also shown with the anti-oestrogen 4OH-tamoxifen and mTOR inhibitor everolimus in ER + breast cancer cells that are sensitive to oestrogen deprivation or everolimus treatment. SOX2OT overexpression decreased BiP and PERK expression. This effect of SOX2OT overexpression was confirmed on BiP and PERK pathway by q-PCR. Our results show that a long noncoding RNA regulates the UPR and evince a new function of SOX2OT as a participant of ER stress reprogramming of breast cancer cells.