SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer
Endoplasmic reticulum (ENR) 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 noncodin...
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MDPI AG
2021-05-01
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| author | Carole Ferraro-Peyret Marjan E. Askarian-Amiri Debina Sarkar Wayne R. Joseph Herah Hansji Bruce C. Baguley Euphemia Y. Leung |
| author_facet | Carole Ferraro-Peyret Marjan E. Askarian-Amiri Debina Sarkar Wayne R. Joseph Herah Hansji Bruce C. Baguley Euphemia Y. Leung |
| author_sort | Carole Ferraro-Peyret |
| collection | DOAJ |
| description | Endoplasmic reticulum (ENR) 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 <i>SOX2</i> overlapping transcript (<i>SOX2OT</i>) are upregulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and <i>SOX2OT</i> expression and the effect of <i>SOX2OT</i> on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation upregulates <i>SOX2OT</i> expression. This upregulation 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. <i>SOX2OT</i> overexpression decreased BiP and PERK expression. This effect of <i>SOX2OT</i> 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 <i>SOX2OT</i> as a participant of ENR stress reprogramming of breast cancer cells. |
| first_indexed | 2024-03-10T11:02:31Z |
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| id | doaj.art-8253ed9cae2f4b4ba4579bf94d976640 |
| institution | Directory Open Access Journal |
| issn | 2413-4155 |
| language | English |
| last_indexed | 2024-03-10T11:02:31Z |
| publishDate | 2021-05-01 |
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| series | Sci |
| spelling | doaj.art-8253ed9cae2f4b4ba4579bf94d9766402023-11-21T21:24:23ZengMDPI AGSci2413-41552021-05-01322610.3390/sci3020026SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast CancerCarole Ferraro-Peyret0Marjan E. Askarian-Amiri1Debina Sarkar2Wayne R. Joseph3Herah Hansji4Bruce C. Baguley5Euphemia Y. Leung6Auckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandAuckland Cancer Society Research Centre, University of Auckland, 85 Park Rd, Grafton, Auckland 1023, New ZealandEndoplasmic reticulum (ENR) 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 <i>SOX2</i> overlapping transcript (<i>SOX2OT</i>) are upregulated in oestrogen receptor-positive (ER+) breast cancer and in response to oestrogen deprivation. We examined the effect of the UPR on SOX2 and <i>SOX2OT</i> expression and the effect of <i>SOX2OT</i> on UPR pathways in breast cancer cell lines. The induction of the UPR by thapsigargin or glucose deprivation upregulates <i>SOX2OT</i> expression. This upregulation 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. <i>SOX2OT</i> overexpression decreased BiP and PERK expression. This effect of <i>SOX2OT</i> 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 <i>SOX2OT</i> as a participant of ENR stress reprogramming of breast cancer cells.https://www.mdpi.com/2413-4155/3/2/26breast cancerLncRNASOX2OTSOX2UPR4-OH tamoxifen |
| spellingShingle | Carole Ferraro-Peyret Marjan E. Askarian-Amiri Debina Sarkar Wayne R. Joseph Herah Hansji Bruce C. Baguley Euphemia Y. Leung SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer Sci breast cancer LncRNA SOX2OT SOX2 UPR 4-OH tamoxifen |
| title | SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer |
| title_full | SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer |
| title_fullStr | SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer |
| title_full_unstemmed | SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer |
| title_short | SOX2OT Long Noncoding RNA Is Regulated by the UPR in Oestrogen Receptor-Positive Breast Cancer |
| title_sort | sox2ot long noncoding rna is regulated by the upr in oestrogen receptor positive breast cancer |
| topic | breast cancer LncRNA SOX2OT SOX2 UPR 4-OH tamoxifen |
| url | https://www.mdpi.com/2413-4155/3/2/26 |
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