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Open AccessArticlePost Publication Peer ReviewVersion 1, Original

SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer (Version 1, Original)

1
Auckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New Zealand
2
Univ Lyon, ISPB Faculty of Pharmacy, INSERM 1052, CNRS5286, Cancer Research Centre of Lyon, F-69008 Lyon, France
3
Hospices Civils de Lyon, Biopathology of Tumours, GHE Hospital, F-69500 Bron, France
4
Molecular Medicine and Pathology Department, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New Zealand
5
Biochemistry Department, University of Otago, 710 Cumberland Street, Dunedin North, Dunedin 9016, New Zealand
6
Murdoch Children’s Research Institute, The Royal Children’s Hospital, Flemington Rd, Parkville, VIC 3052, Australia
*
Authors to whom correspondence should be addressed.
Received: 6 March 2020 / Accepted: 20 March 2020 / Published: 6 April 2020
Peer review status: 1st round review Read review reports Apply as reviewer

Reviewer 1 Ming-Yang Wang Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan Reviewer 2
Version 1
Original
Not approved Reviewer inviting
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. View Full-Text
Keywords: breast cancer; LncRNA; SOX2OT; SOX2; UPR; 4-OH tamoxifen breast cancer; LncRNA; SOX2OT; SOX2; UPR; 4-OH tamoxifen
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Ferraro-Peyret, C.; Askarian-Amiri, M.E.; Sarkar, D.; Joseph, W.R.; Hansji, H.; Baguley, B.C.; Leung, E.Y. SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer. Sci 2020, 2, 24.

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1

Reviewer 1

Sent on 29 Jun 2020 by Ming-Yang Wang | Not approved
Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan

the study only design overexpression of the related gene to explain the phenomena observe. it provide clue to the function. However, it would be more scientific sound to include gene knockdown or knockout data to support the conclusion. 

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